Datasets:

MedRAG
/

textbooks

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 126k rows

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.

id stringlengths 14 28	title stringclasses 18 values	content stringlengths 2 999	contents stringlengths 19 1.02k
Cell_Biology_Alberts_1210	Cell_Biology_Alberts	origins of replication telomere centromere telomere Figure 5–30 The origins of DNA replication on chromosome III of the yeast S. cerevisiae. This chromosome, one of the smallest eukaryotic chromosomes known, carries a total of 180 genes. As indicated, it contains 18 replication origins, although they are used with different frequencies. Those in red are typically used in less than 10% of cell divisions, while those in green are used about 90% of the time.	Cell_Biology_Alberts. origins of replication telomere centromere telomere Figure 5–30 The origins of DNA replication on chromosome III of the yeast S. cerevisiae. This chromosome, one of the smallest eukaryotic chromosomes known, carries a total of 180 genes. As indicated, it contains 18 replication origins, although they are used with different frequencies. Those in red are typically used in less than 10% of cell divisions, while those in green are used about 90% of the time.
Cell_Biology_Alberts_1211	Cell_Biology_Alberts	Figure 5–31 DNA replication initiation in eukaryotes. This mechanism ensures that each origin of replication is activated only once per cell cycle. An origin of replication can be used only if a prereplicative complex forms there in G1 phase. At the beginning of S phase, specialized kinases phosphorylate Mcm and ORC, activating the former and inactivating the latter. A new prereplicative complex cannot form at the origin until the cell progresses to the next G1 phase, when the bound ORC has been dephosphorylated. Note that the eukaryotic Mcm helicase moves along the leading-strand template, whereas the bacterial helicase moves along the lagging-strand template (see Figure 5–25). As the forks begin to move, ORC is displaced, and new ORCs rapidly bind to the newly replicated origins.	Cell_Biology_Alberts. Figure 5–31 DNA replication initiation in eukaryotes. This mechanism ensures that each origin of replication is activated only once per cell cycle. An origin of replication can be used only if a prereplicative complex forms there in G1 phase. At the beginning of S phase, specialized kinases phosphorylate Mcm and ORC, activating the former and inactivating the latter. A new prereplicative complex cannot form at the origin until the cell progresses to the next G1 phase, when the bound ORC has been dephosphorylated. Note that the eukaryotic Mcm helicase moves along the leading-strand template, whereas the bacterial helicase moves along the lagging-strand template (see Figure 5–25). As the forks begin to move, ORC is displaced, and new ORCs rapidly bind to the newly replicated origins.
Cell_Biology_Alberts_1212	Cell_Biology_Alberts	The protein kinases that trigger DNA replication simultaneously prevent assembly of new prereplicative complexes until the next M phase resets the entire cycle (for details, see pp. 974–975). They do this, in part, by phosphorylating ORC, rendering it unable to accept new helicases. This strategy provides a single window of opportunity for prereplicative complexes to form (G1 phase, when kinase activity is low) and a second window for them to be activated and subsequently disassembled (S phase, when kinase activity is high). Because these two phases of the cell cycle are mutually exclusive and occur in a prescribed order, each origin of replication can fire once and only once during each cell cycle. Features of the Human Genome That Specify Origins of Replication Remain to Be Discovered	Cell_Biology_Alberts. The protein kinases that trigger DNA replication simultaneously prevent assembly of new prereplicative complexes until the next M phase resets the entire cycle (for details, see pp. 974–975). They do this, in part, by phosphorylating ORC, rendering it unable to accept new helicases. This strategy provides a single window of opportunity for prereplicative complexes to form (G1 phase, when kinase activity is low) and a second window for them to be activated and subsequently disassembled (S phase, when kinase activity is high). Because these two phases of the cell cycle are mutually exclusive and occur in a prescribed order, each origin of replication can fire once and only once during each cell cycle. Features of the Human Genome That Specify Origins of Replication Remain to Be Discovered
Cell_Biology_Alberts_1213	Cell_Biology_Alberts	Features of the Human Genome That Specify Origins of Replication Remain to Be Discovered Compared with the situation in budding yeast, the determinants of replication origins in other eukaryotes have been difficult to discover. It has been possible to identify specific human DNA sequences, each several thousand nucleotide pairs in length, that are sufficient to serve as replication origins. These origins continue to function when moved to a different chromosomal region by recombinant DNA methods, as long as they are placed in a region where the chromatin is relatively uncondensed. However, comparisons of such DNA sequences have not revealed specific DNA sequences that mark origins of replication.	Cell_Biology_Alberts. Features of the Human Genome That Specify Origins of Replication Remain to Be Discovered Compared with the situation in budding yeast, the determinants of replication origins in other eukaryotes have been difficult to discover. It has been possible to identify specific human DNA sequences, each several thousand nucleotide pairs in length, that are sufficient to serve as replication origins. These origins continue to function when moved to a different chromosomal region by recombinant DNA methods, as long as they are placed in a region where the chromatin is relatively uncondensed. However, comparisons of such DNA sequences have not revealed specific DNA sequences that mark origins of replication.
Cell_Biology_Alberts_1214	Cell_Biology_Alberts	Despite this, a human ORC that is very similar to the yeast ORC binds to origins of replication and initiates DNA replication in humans. Many of the other proteins that function in the initiation process in yeast likewise have central roles in humans. It therefore seems likely that the yeast and human initiation mechanisms are similar in outline, but chromatin structure, transcriptional activity, or some property of the genome other than a specific DNA sequence has the central role in attracting ORC and specifying mammalian origins of replication. These ideas could also help to explain how a given mammalian cell chooses which of the many possible origins to use when it replicates its genome and how this choice could differ from cell to cell. Clearly, we have a great deal to discover about the fundamental process of DNA replication initiation. New Nucleosomes Are Assembled Behind the Replication Fork	Cell_Biology_Alberts. Despite this, a human ORC that is very similar to the yeast ORC binds to origins of replication and initiates DNA replication in humans. Many of the other proteins that function in the initiation process in yeast likewise have central roles in humans. It therefore seems likely that the yeast and human initiation mechanisms are similar in outline, but chromatin structure, transcriptional activity, or some property of the genome other than a specific DNA sequence has the central role in attracting ORC and specifying mammalian origins of replication. These ideas could also help to explain how a given mammalian cell chooses which of the many possible origins to use when it replicates its genome and how this choice could differ from cell to cell. Clearly, we have a great deal to discover about the fundamental process of DNA replication initiation. New Nucleosomes Are Assembled Behind the Replication Fork
Cell_Biology_Alberts_1215	Cell_Biology_Alberts	Several additional aspects of DNA replication are specific to eukaryotes. As discussed in Chapter 4, eukaryotic chromosomes are composed of roughly equal mixtures of DNA and protein. Chromosome duplication therefore requires not only the replication of DNA, but also the synthesis and assembly of new chromosomal proteins onto the DNA behind each replication fork. Although we are far from understanding this process in detail, we are beginning to learn how the fundamental unit of chromatin packaging, the nucleosome, is duplicated. The cell requires a large amount of new histone protein, approximately equal in mass to the newly synthesized DNA, to make the new nucleosomes in each cell cycle. For this reason, most eukaryotic organisms possess multiple copies of the gene for each histone. Vertebrate cells, for example, have about 20 repeated gene sets, most containing the genes that encode all five histones (H1, H2A, H2B, H3, and H4).	Cell_Biology_Alberts. Several additional aspects of DNA replication are specific to eukaryotes. As discussed in Chapter 4, eukaryotic chromosomes are composed of roughly equal mixtures of DNA and protein. Chromosome duplication therefore requires not only the replication of DNA, but also the synthesis and assembly of new chromosomal proteins onto the DNA behind each replication fork. Although we are far from understanding this process in detail, we are beginning to learn how the fundamental unit of chromatin packaging, the nucleosome, is duplicated. The cell requires a large amount of new histone protein, approximately equal in mass to the newly synthesized DNA, to make the new nucleosomes in each cell cycle. For this reason, most eukaryotic organisms possess multiple copies of the gene for each histone. Vertebrate cells, for example, have about 20 repeated gene sets, most containing the genes that encode all five histones (H1, H2A, H2B, H3, and H4).
Cell_Biology_Alberts_1216	Cell_Biology_Alberts	Unlike most proteins, which are made continuously, histones are synthesized mainly in S phase, when the level of histone mRNA increases about fiftyfold as a result of both increased transcription and decreased mRNA degradation. The major histone mRNAs are degraded within minutes when DNA synthesis stops at the end of S phase. The mechanism depends on special properties of the 3ʹends of these mRNAs, as discussed in Chapter 7. In contrast, the histone proteins themselves are remarkably stable and may survive for the entire life of a cell. The tight linkage between DNA synthesis and histone synthesis appears to reflect a feedback mechanism that monitors the level of free histone to ensure that the amount of histone made exactly matches the amount of new DNA synthesized.	Cell_Biology_Alberts. Unlike most proteins, which are made continuously, histones are synthesized mainly in S phase, when the level of histone mRNA increases about fiftyfold as a result of both increased transcription and decreased mRNA degradation. The major histone mRNAs are degraded within minutes when DNA synthesis stops at the end of S phase. The mechanism depends on special properties of the 3ʹends of these mRNAs, as discussed in Chapter 7. In contrast, the histone proteins themselves are remarkably stable and may survive for the entire life of a cell. The tight linkage between DNA synthesis and histone synthesis appears to reflect a feedback mechanism that monitors the level of free histone to ensure that the amount of histone made exactly matches the amount of new DNA synthesized.
Cell_Biology_Alberts_1217	Cell_Biology_Alberts	As a replication fork advances, it must pass through the parental nucleosomes. In the cell, efficient replication requires chromatin remodeling complexes (discussed in Chapter 4) to destabilize the DNA–histone interfaces. Aided by such complexes, replication forks can transit even highly condensed chromatin efficiently.	Cell_Biology_Alberts. As a replication fork advances, it must pass through the parental nucleosomes. In the cell, efficient replication requires chromatin remodeling complexes (discussed in Chapter 4) to destabilize the DNA–histone interfaces. Aided by such complexes, replication forks can transit even highly condensed chromatin efficiently.
Cell_Biology_Alberts_1218	Cell_Biology_Alberts	As a replication fork passes through chromatin, the histones are transiently displaced leaving about 600 nucleotide pairs of non-nucleosomal DNA in its wake. The reestablishment of nucleosomes behind a moving fork occurs in an intriguing way. When a nucleosome is traversed by a replication fork, the histone octamer appears to be broken into an H3-H4 tetramer and two H2A-H2B dimers (discussed in Chapter 4). The H3-H4 tetramer remains loosely associated with DNA and is distributed at random to one or the other daughter duplex, but the H2A-H2B dimers are released completely from DNA. Freshly made H3-H4 tetramers are added to the newly synthesized DNA to fill in the “spaces,” and H2A-H2B dimers—half of which are old and half new—are then added at random to complete the nucleosomes (Figure 5–32). The formation of new nucleosomes behind a replication fork has an important consequence for the process of DNA replication itself. As DNA polymerase δ discontinuously synthesizes the lagging	Cell_Biology_Alberts. As a replication fork passes through chromatin, the histones are transiently displaced leaving about 600 nucleotide pairs of non-nucleosomal DNA in its wake. The reestablishment of nucleosomes behind a moving fork occurs in an intriguing way. When a nucleosome is traversed by a replication fork, the histone octamer appears to be broken into an H3-H4 tetramer and two H2A-H2B dimers (discussed in Chapter 4). The H3-H4 tetramer remains loosely associated with DNA and is distributed at random to one or the other daughter duplex, but the H2A-H2B dimers are released completely from DNA. Freshly made H3-H4 tetramers are added to the newly synthesized DNA to fill in the “spaces,” and H2A-H2B dimers—half of which are old and half new—are then added at random to complete the nucleosomes (Figure 5–32). The formation of new nucleosomes behind a replication fork has an important consequence for the process of DNA replication itself. As DNA polymerase δ discontinuously synthesizes the lagging
Cell_Biology_Alberts_1219	Cell_Biology_Alberts	5–32). The formation of new nucleosomes behind a replication fork has an important consequence for the process of DNA replication itself. As DNA polymerase δ discontinuously synthesizes the lagging strand (see pp. 253–254), the length of each Okazaki fragment is determined by the point at which DNA polymerase δ is blocked by a newly formed nucleosome. This tight coupling between nucleosome duplication and DNA replication explains why the length of Okazaki fragments in eukaryotes (~200 nucleotides) is approximately the same as the nucleosome repeat length.	Cell_Biology_Alberts. 5–32). The formation of new nucleosomes behind a replication fork has an important consequence for the process of DNA replication itself. As DNA polymerase δ discontinuously synthesizes the lagging strand (see pp. 253–254), the length of each Okazaki fragment is determined by the point at which DNA polymerase δ is blocked by a newly formed nucleosome. This tight coupling between nucleosome duplication and DNA replication explains why the length of Okazaki fragments in eukaryotes (~200 nucleotides) is approximately the same as the nucleosome repeat length.
Cell_Biology_Alberts_1220	Cell_Biology_Alberts	262 Chapter 5: DNA Replication, Repair, and Recombination H2A-H2B dimer displaced in front of replication fork The orderly and rapid addition of new H3-H4 tetramers and H2A-H2B dimers behind a replication fork requires histone chaperones (also called chromatin assembly factors). These multisubunit complexes bind the highly basic histones and release them for assembly only in the appropriate context. The histone chaperones, along with their cargoes, are directed to newly replicated DNA through a specific interaction with the eukaryotic sliding clamp called PCNA (see Figure 5–32B). These clamps are left behind moving replication forks and remain on the DNA long enough for the histone chaperones to complete their tasks. Telomerase Replicates the Ends of Chromosomes	Cell_Biology_Alberts. 262 Chapter 5: DNA Replication, Repair, and Recombination H2A-H2B dimer displaced in front of replication fork The orderly and rapid addition of new H3-H4 tetramers and H2A-H2B dimers behind a replication fork requires histone chaperones (also called chromatin assembly factors). These multisubunit complexes bind the highly basic histones and release them for assembly only in the appropriate context. The histone chaperones, along with their cargoes, are directed to newly replicated DNA through a specific interaction with the eukaryotic sliding clamp called PCNA (see Figure 5–32B). These clamps are left behind moving replication forks and remain on the DNA long enough for the histone chaperones to complete their tasks. Telomerase Replicates the Ends of Chromosomes
Cell_Biology_Alberts_1221	Cell_Biology_Alberts	Telomerase Replicates the Ends of Chromosomes We saw earlier that synthesis of the lagging strand at a replication fork must occur discontinuously through a backstitching mechanism that produces short DNA fragments. This mechanism encounters a special problem when the replication fork reaches an end of a linear chromosome. The final RNA primer synthesized on the lagging-strand template cannot be replaced by DNA because there is no 3ʹ-OH end available for the repair polymerase. Without a mechanism to deal with this problem, DNA would be lost from the ends of all chromosomes each time a cell divides.	Cell_Biology_Alberts. Telomerase Replicates the Ends of Chromosomes We saw earlier that synthesis of the lagging strand at a replication fork must occur discontinuously through a backstitching mechanism that produces short DNA fragments. This mechanism encounters a special problem when the replication fork reaches an end of a linear chromosome. The final RNA primer synthesized on the lagging-strand template cannot be replaced by DNA because there is no 3ʹ-OH end available for the repair polymerase. Without a mechanism to deal with this problem, DNA would be lost from the ends of all chromosomes each time a cell divides.
Cell_Biology_Alberts_1222	Cell_Biology_Alberts	Bacteria solve this “end-replication” problem by having circular DNA molecules as chromosomes (see Figure 5–24). Eukaryotes solve it in a different way: they have specialized nucleotide sequences at the ends of their chromosomes that are incorporated into structures called telomeres (discussed in Chapter 4). Telomeres contain many tandem repeats of a short sequence that is similar in organisms as diverse as protozoa, fungi, plants, and mammals. In humans, the sequence of the repeat unit is GGGTTA, and it is repeated roughly a thousand times at each telomere.	Cell_Biology_Alberts. Bacteria solve this “end-replication” problem by having circular DNA molecules as chromosomes (see Figure 5–24). Eukaryotes solve it in a different way: they have specialized nucleotide sequences at the ends of their chromosomes that are incorporated into structures called telomeres (discussed in Chapter 4). Telomeres contain many tandem repeats of a short sequence that is similar in organisms as diverse as protozoa, fungi, plants, and mammals. In humans, the sequence of the repeat unit is GGGTTA, and it is repeated roughly a thousand times at each telomere.
Cell_Biology_Alberts_1223	Cell_Biology_Alberts	Telomere DNA sequences are recognized by sequence-specific DNA-binding proteins that attract an enzyme, called telomerase, that replenishes these sequences each time a cell divides. Telomerase recognizes the tip of an existing telomere DNA repeat sequence and elongates it in the 5ʹ-to-3ʹ direction, using an RNA template that is a component of the enzyme itself to synthesize new copies of the repeat (Figure 5–33). The enzymatic portion of telomerase resembles other reverse transcriptases, proteins that synthesize DNA using an RNA template, although, in this case, the telomerase RNA also contributes functional groups to make the catalysis more efficient. After extension of the parental DNA strand by telomerase, replication of the lagging strand at the chromosome end can be completed by the conventional DNA polymerases, using these extensions as a template to synthesize the complementary strand (Figure 5–34).	Cell_Biology_Alberts. Telomere DNA sequences are recognized by sequence-specific DNA-binding proteins that attract an enzyme, called telomerase, that replenishes these sequences each time a cell divides. Telomerase recognizes the tip of an existing telomere DNA repeat sequence and elongates it in the 5ʹ-to-3ʹ direction, using an RNA template that is a component of the enzyme itself to synthesize new copies of the repeat (Figure 5–33). The enzymatic portion of telomerase resembles other reverse transcriptases, proteins that synthesize DNA using an RNA template, although, in this case, the telomerase RNA also contributes functional groups to make the catalysis more efficient. After extension of the parental DNA strand by telomerase, replication of the lagging strand at the chromosome end can be completed by the conventional DNA polymerases, using these extensions as a template to synthesize the complementary strand (Figure 5–34).
Cell_Biology_Alberts_1224	Cell_Biology_Alberts	Figure 5–32 Formation of nucleosomes behind a replication fork. Parental H3-H4 tetramers are distributed at random to the daughter DNA molecules, with roughly equal numbers inherited by each daughter. In contrast, H2A-H2B dimers are released from the DNA as the replication fork passes. This release begins just in front of the replication fork and is facilitated by chromatin remodeling complexes that move with the fork. Histone chaperones (NAP1 and CAF1) restore the full complement of histones to daughter molecules using both parental and newly synthesized histones. Although some daughter nucleosomes contain only parental histones or only newly synthesized histones, most are hybrids of old and new. For simplicity, the DNA double helix shown as a single red line. (Adapted from J.D. Watson et al., Molecular Biology of the Gene, 5th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2004.) remainder of telomerase proteintelomerase RNA region of telomerase RNA used as	Cell_Biology_Alberts. Figure 5–32 Formation of nucleosomes behind a replication fork. Parental H3-H4 tetramers are distributed at random to the daughter DNA molecules, with roughly equal numbers inherited by each daughter. In contrast, H2A-H2B dimers are released from the DNA as the replication fork passes. This release begins just in front of the replication fork and is facilitated by chromatin remodeling complexes that move with the fork. Histone chaperones (NAP1 and CAF1) restore the full complement of histones to daughter molecules using both parental and newly synthesized histones. Although some daughter nucleosomes contain only parental histones or only newly synthesized histones, most are hybrids of old and new. For simplicity, the DNA double helix shown as a single red line. (Adapted from J.D. Watson et al., Molecular Biology of the Gene, 5th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2004.) remainder of telomerase proteintelomerase RNA region of telomerase RNA used as
Cell_Biology_Alberts_1225	Cell_Biology_Alberts	Watson et al., Molecular Biology of the Gene, 5th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2004.) remainder of telomerase proteintelomerase RNA region of telomerase RNA used as template “palm“—active site of telomerase protein rest of synthesized chromosome telomere DNA	Cell_Biology_Alberts. Watson et al., Molecular Biology of the Gene, 5th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2004.) remainder of telomerase proteintelomerase RNA region of telomerase RNA used as template “palm“—active site of telomerase protein rest of synthesized chromosome telomere DNA
Cell_Biology_Alberts_1226	Cell_Biology_Alberts	Telomeres Are Packaged Into Specialized Structures That Protect the Ends of Chromosomes The ends of chromosomes present cells with an additional problem. As we will see in the next part of this chapter, when a chromosome is accidently broken, the break is rapidly repaired (see Figure 5–45). Telomeres must clearly be distinguished from these accidental breaks; otherwise the cell will attempt to “repair” telomeres, causing chromosome fusions and other genetic abnormalities. Telomeres have several features to prevent this from happening.	Cell_Biology_Alberts. Telomeres Are Packaged Into Specialized Structures That Protect the Ends of Chromosomes The ends of chromosomes present cells with an additional problem. As we will see in the next part of this chapter, when a chromosome is accidently broken, the break is rapidly repaired (see Figure 5–45). Telomeres must clearly be distinguished from these accidental breaks; otherwise the cell will attempt to “repair” telomeres, causing chromosome fusions and other genetic abnormalities. Telomeres have several features to prevent this from happening.
Cell_Biology_Alberts_1227	Cell_Biology_Alberts	A specialized nuclease chews back the 5ʹend of a telomere leaving a protruding single-strand end. This protruding end—in combination with the GGGTTA repeats in telomeres—attracts a group of proteins that form a protective chromosome cap known as shelterin. In particular, shelterin “hides” telomeres from the cell’s damage detectors that continually monitor DNA. When human telomeres are artificially cross-linked and viewed by electron microscopy, structures known as “t-loops” are observed in which the protruding end of the telomere loops back and tucks itself into the duplex DNA of the telomere repeat sequence (Figure 5–35). It is believed that t-loops are regulated by shelterin and provide additional protection for the ends of chromosomes. incomplete, newly synthesized lagging strand direction of AACCCC telomere 5˜ synthesisTELOMERASE EXTENDS 3˜ END telomerase with bound RNA template	Cell_Biology_Alberts. A specialized nuclease chews back the 5ʹend of a telomere leaving a protruding single-strand end. This protruding end—in combination with the GGGTTA repeats in telomeres—attracts a group of proteins that form a protective chromosome cap known as shelterin. In particular, shelterin “hides” telomeres from the cell’s damage detectors that continually monitor DNA. When human telomeres are artificially cross-linked and viewed by electron microscopy, structures known as “t-loops” are observed in which the protruding end of the telomere loops back and tucks itself into the duplex DNA of the telomere repeat sequence (Figure 5–35). It is believed that t-loops are regulated by shelterin and provide additional protection for the ends of chromosomes. incomplete, newly synthesized lagging strand direction of AACCCC telomere 5˜ synthesisTELOMERASE EXTENDS 3˜ END telomerase with bound RNA template
Cell_Biology_Alberts_1228	Cell_Biology_Alberts	incomplete, newly synthesized lagging strand direction of AACCCC telomere 5˜ synthesisTELOMERASE EXTENDS 3˜ END telomerase with bound RNA template Figure 5–33 Structure of a portion of telomerase. Telomerase is a large protein– RNA complex. The RNA (blue) contains a templating sequence for synthesizing new DNA telomere repeats. The synthesis reaction itself is carried out by the reverse transcriptase domain of the protein, shown in green. A reverse transcriptase is a special form of polymerase enzyme that uses an RNA template to make a DNA strand; telomerase is unique in carrying its own RNA template with it. Telomerase also has several additional protein domains (not shown) that are needed to assemble the enzyme at the ends of chromosomes. (Modified from J. Lingner and T.R. Cech, Curr. Opin. Genet. Dev. 8:226–232, 1998. With permission from Elsevier.)	Cell_Biology_Alberts. incomplete, newly synthesized lagging strand direction of AACCCC telomere 5˜ synthesisTELOMERASE EXTENDS 3˜ END telomerase with bound RNA template Figure 5–33 Structure of a portion of telomerase. Telomerase is a large protein– RNA complex. The RNA (blue) contains a templating sequence for synthesizing new DNA telomere repeats. The synthesis reaction itself is carried out by the reverse transcriptase domain of the protein, shown in green. A reverse transcriptase is a special form of polymerase enzyme that uses an RNA template to make a DNA strand; telomerase is unique in carrying its own RNA template with it. Telomerase also has several additional protein domains (not shown) that are needed to assemble the enzyme at the ends of chromosomes. (Modified from J. Lingner and T.R. Cech, Curr. Opin. Genet. Dev. 8:226–232, 1998. With permission from Elsevier.)
Cell_Biology_Alberts_1229	Cell_Biology_Alberts	Figure 5–34 Telomere replication. Shown here are the reactions that synthesize the repeating sequences that form the ends of the chromosomes (telomeres) of diverse eukaryotic organisms. The 3ʹ end of the parental DNA strand is extended by RNA-templated DNA synthesis; this allows the incomplete daughter DNA strand that is paired with it to be extended in its 5ʹ direction. This incomplete, lagging strand is presumed to be completed by DNA polymerase α, which carries a DNA primase as one of its subunits (Movie 5.6). The telomere sequence illustrated is that of the ciliate Tetrahymena, in which these reactions were first discovered. Because the processes that grow and shrink each telomere sequence are only approximately balanced, a chromosome end contains a variable number of telomeric repeats. Not surprisingly, many cells have homeostatic mechanisms that maintain the number of these repeats within a limited range (Figure 5–36).	Cell_Biology_Alberts. Figure 5–34 Telomere replication. Shown here are the reactions that synthesize the repeating sequences that form the ends of the chromosomes (telomeres) of diverse eukaryotic organisms. The 3ʹ end of the parental DNA strand is extended by RNA-templated DNA synthesis; this allows the incomplete daughter DNA strand that is paired with it to be extended in its 5ʹ direction. This incomplete, lagging strand is presumed to be completed by DNA polymerase α, which carries a DNA primase as one of its subunits (Movie 5.6). The telomere sequence illustrated is that of the ciliate Tetrahymena, in which these reactions were first discovered. Because the processes that grow and shrink each telomere sequence are only approximately balanced, a chromosome end contains a variable number of telomeric repeats. Not surprisingly, many cells have homeostatic mechanisms that maintain the number of these repeats within a limited range (Figure 5–36).
Cell_Biology_Alberts_1230	Cell_Biology_Alberts	In most of the dividing somatic cells of humans, however, telomeres gradually shorten, and it has been proposed that this provides a counting mechanism that helps prevent the unlimited proliferation of wayward cells in adult tissues. In its simplest form, this idea holds that our somatic cells start off in the embryo with a full complement of telomeric repeats. These are then eroded to different extents in different cell types. Some stem cells, notably those in tissues that must be replenished at a high rate throughout life—bone marrow or gut lining, for example— retain full telomerase activity. However, in many other types of cells, the level of telomerase is turned down so that the enzyme cannot quite keep up with chromosome duplication. Such cells lose 100–200 nucleotides from each telomere every time they divide. After many cell generations, the descendant cells will inherit chromosomes that lack telomere function, and, as a result of this defect, activate a DNA-damage response	Cell_Biology_Alberts. In most of the dividing somatic cells of humans, however, telomeres gradually shorten, and it has been proposed that this provides a counting mechanism that helps prevent the unlimited proliferation of wayward cells in adult tissues. In its simplest form, this idea holds that our somatic cells start off in the embryo with a full complement of telomeric repeats. These are then eroded to different extents in different cell types. Some stem cells, notably those in tissues that must be replenished at a high rate throughout life—bone marrow or gut lining, for example— retain full telomerase activity. However, in many other types of cells, the level of telomerase is turned down so that the enzyme cannot quite keep up with chromosome duplication. Such cells lose 100–200 nucleotides from each telomere every time they divide. After many cell generations, the descendant cells will inherit chromosomes that lack telomere function, and, as a result of this defect, activate a DNA-damage response
Cell_Biology_Alberts_1231	Cell_Biology_Alberts	every time they divide. After many cell generations, the descendant cells will inherit chromosomes that lack telomere function, and, as a result of this defect, activate a DNA-damage response causing them to withdraw permanently from the cell cycle and cease dividing—a process called replicative cell senescence (discussed in Chapter 17). In theory, such a mechanism could provide a safeguard against the uncontrolled cell proliferation of abnormal cells in somatic tissues, thereby helping to protect us from cancer.	Cell_Biology_Alberts. every time they divide. After many cell generations, the descendant cells will inherit chromosomes that lack telomere function, and, as a result of this defect, activate a DNA-damage response causing them to withdraw permanently from the cell cycle and cease dividing—a process called replicative cell senescence (discussed in Chapter 17). In theory, such a mechanism could provide a safeguard against the uncontrolled cell proliferation of abnormal cells in somatic tissues, thereby helping to protect us from cancer.
Cell_Biology_Alberts_1232	Cell_Biology_Alberts	fraction of chromosome ends Figure 5–35 A t-loop at the end of a mammalian chromosome. (A) Electron micrograph of the DNA at the end of an interphase human chromosome. The chromosome was fixed, deproteinated, and artificially thickened before viewing. The loop seen here is approximately 15,000 nucleotide pairs in length. (B) Structure of a t-loop. The insertion of the single-strand 3ʹ end into the duplex repeats is carried out, and the structure maintained, by specialized proteins. (From J.D. Griffith et al., Cell 97:503–514, 1999. With permission from Elsevier.)	Cell_Biology_Alberts. fraction of chromosome ends Figure 5–35 A t-loop at the end of a mammalian chromosome. (A) Electron micrograph of the DNA at the end of an interphase human chromosome. The chromosome was fixed, deproteinated, and artificially thickened before viewing. The loop seen here is approximately 15,000 nucleotide pairs in length. (B) Structure of a t-loop. The insertion of the single-strand 3ʹ end into the duplex repeats is carried out, and the structure maintained, by specialized proteins. (From J.D. Griffith et al., Cell 97:503–514, 1999. With permission from Elsevier.)
Cell_Biology_Alberts_1233	Cell_Biology_Alberts	Figure 5–36 A demonstration that yeast cells control the length of their telomeres. In this experiment, the telomere at one end of a particular chromosome is artificially made either longer (left) or shorter (right) than average. After many cell divisions, the chromosome recovers, showing an average telomere length and a length distribution that is typical of the other chromosomes in the yeast cell. A similar feedback mechanism for controlling telomere length has been proposed for the germ-line cells of animals.	Cell_Biology_Alberts. Figure 5–36 A demonstration that yeast cells control the length of their telomeres. In this experiment, the telomere at one end of a particular chromosome is artificially made either longer (left) or shorter (right) than average. After many cell divisions, the chromosome recovers, showing an average telomere length and a length distribution that is typical of the other chromosomes in the yeast cell. A similar feedback mechanism for controlling telomere length has been proposed for the germ-line cells of animals.
Cell_Biology_Alberts_1234	Cell_Biology_Alberts	The idea that telomere length acts as a “measuring stick” to count cell divisions and thereby regulate the lifetime of the cell lineage has been tested in several ways. For certain types of human cells grown in tissue culture, the experimental results support such a theory. Human fibroblasts normally proliferate for about 60 cell divisions in culture before undergoing replicative cell senescence. Like most other somatic cells in humans, fibroblasts produce only low levels of telomerase, and their telomeres gradually shorten each time they divide. When telomerase is provided to the fibroblasts by inserting an active telomerase gene, telomere length is maintained and many of the cells now continue to proliferate indefinitely.	Cell_Biology_Alberts. The idea that telomere length acts as a “measuring stick” to count cell divisions and thereby regulate the lifetime of the cell lineage has been tested in several ways. For certain types of human cells grown in tissue culture, the experimental results support such a theory. Human fibroblasts normally proliferate for about 60 cell divisions in culture before undergoing replicative cell senescence. Like most other somatic cells in humans, fibroblasts produce only low levels of telomerase, and their telomeres gradually shorten each time they divide. When telomerase is provided to the fibroblasts by inserting an active telomerase gene, telomere length is maintained and many of the cells now continue to proliferate indefinitely.
Cell_Biology_Alberts_1235	Cell_Biology_Alberts	It has been proposed that this type of control on cell proliferation may contribute to the aging of animals like ourselves. These ideas have been tested by producing transgenic mice that lack telomerase entirely. The telomeres in mouse chromosomes are about five times longer than human telomeres, and the mice must therefore be bred through three or more generations before their telomeres have shrunk to the normal human length. It is therefore perhaps not surprising that the first generations of mice develop normally. However, the mice in later generations develop progressively more defects in some of their highly proliferative tissues. In addition, these mice show signs of premature aging and have a pronounced tendency to develop tumors. In these and other respects these mice resemble humans with the genetic disease dyskeratosis congenita. Individuals afflicted with this disease carry one functional and one nonfunctional copy of the telomerase RNA gene; they have prematurely shortened	Cell_Biology_Alberts. It has been proposed that this type of control on cell proliferation may contribute to the aging of animals like ourselves. These ideas have been tested by producing transgenic mice that lack telomerase entirely. The telomeres in mouse chromosomes are about five times longer than human telomeres, and the mice must therefore be bred through three or more generations before their telomeres have shrunk to the normal human length. It is therefore perhaps not surprising that the first generations of mice develop normally. However, the mice in later generations develop progressively more defects in some of their highly proliferative tissues. In addition, these mice show signs of premature aging and have a pronounced tendency to develop tumors. In these and other respects these mice resemble humans with the genetic disease dyskeratosis congenita. Individuals afflicted with this disease carry one functional and one nonfunctional copy of the telomerase RNA gene; they have prematurely shortened
Cell_Biology_Alberts_1236	Cell_Biology_Alberts	with the genetic disease dyskeratosis congenita. Individuals afflicted with this disease carry one functional and one nonfunctional copy of the telomerase RNA gene; they have prematurely shortened telomeres and typically die of progressive bone marrow failure. They also develop lung scarring and liver cirrhosis and show abnormalities in various epidermal structures including skin, hair follicles, and nails.	Cell_Biology_Alberts. with the genetic disease dyskeratosis congenita. Individuals afflicted with this disease carry one functional and one nonfunctional copy of the telomerase RNA gene; they have prematurely shortened telomeres and typically die of progressive bone marrow failure. They also develop lung scarring and liver cirrhosis and show abnormalities in various epidermal structures including skin, hair follicles, and nails.
Cell_Biology_Alberts_1237	Cell_Biology_Alberts	The above observations demonstrate that controlling cell proliferation by telomere shortening poses a risk to an organism, because not all of the cells that begin losing the ends of their chromosomes will stop dividing. Some apparently become genetically unstable, but continue to divide, giving rise to variant cells that can lead to cancer. Clearly, the use of telomere shortening as a regulating mechanism is not foolproof and, like many mechanisms in the cell, seems to strike a balance between benefit and risk. The proteins that initiate DNA replication bind to DNA sequences at a replication origin to catalyze the formation of a replication bubble with two outward-moving replication forks. The process begins when an initiator protein–DNA complex is formed that subsequently loads a DNA helicase onto the DNA template. Other proteins are then added to form the multienzyme “replication machine” that catalyzes DNA synthesis at each replication fork.	Cell_Biology_Alberts. The above observations demonstrate that controlling cell proliferation by telomere shortening poses a risk to an organism, because not all of the cells that begin losing the ends of their chromosomes will stop dividing. Some apparently become genetically unstable, but continue to divide, giving rise to variant cells that can lead to cancer. Clearly, the use of telomere shortening as a regulating mechanism is not foolproof and, like many mechanisms in the cell, seems to strike a balance between benefit and risk. The proteins that initiate DNA replication bind to DNA sequences at a replication origin to catalyze the formation of a replication bubble with two outward-moving replication forks. The process begins when an initiator protein–DNA complex is formed that subsequently loads a DNA helicase onto the DNA template. Other proteins are then added to form the multienzyme “replication machine” that catalyzes DNA synthesis at each replication fork.
Cell_Biology_Alberts_1238	Cell_Biology_Alberts	In bacteria and some simple eukaryotes, replication origins are specified by specific DNA sequences that are only several hundred nucleotide pairs long. In other eukaryotes, such as humans, the sequences needed to specify an origin of DNA replication seem to be less well defined, and the origin can span several thousand nucleotide pairs.	Cell_Biology_Alberts. In bacteria and some simple eukaryotes, replication origins are specified by specific DNA sequences that are only several hundred nucleotide pairs long. In other eukaryotes, such as humans, the sequences needed to specify an origin of DNA replication seem to be less well defined, and the origin can span several thousand nucleotide pairs.
Cell_Biology_Alberts_1239	Cell_Biology_Alberts	Bacteria typically have a single origin of replication in a circular chromosome. With fork speeds of up to 1000 nucleotides per second, they can replicate their genome in less than an hour. Eukaryotic DNA replication takes place in only one part of the cell cycle, the S phase. The replication fork in eukaryotes moves about 10 times more slowly than the bacterial replication fork, and the much longer eukaryotic chromosomes each require many replication origins to complete their replication in an S phase, which typically lasts for 8 hours in human cells. The different replication origins in these eukaryotic chromosomes are activated in a sequence, determined in part by the structure of the chromatin, with the most condensed regions of chromatin typically beginning their replication last. After the replication fork has passed, chromatin structure is re-formed by the addition of new histones to the old histones that are directly inherited by each daughter DNA molecule.	Cell_Biology_Alberts. Bacteria typically have a single origin of replication in a circular chromosome. With fork speeds of up to 1000 nucleotides per second, they can replicate their genome in less than an hour. Eukaryotic DNA replication takes place in only one part of the cell cycle, the S phase. The replication fork in eukaryotes moves about 10 times more slowly than the bacterial replication fork, and the much longer eukaryotic chromosomes each require many replication origins to complete their replication in an S phase, which typically lasts for 8 hours in human cells. The different replication origins in these eukaryotic chromosomes are activated in a sequence, determined in part by the structure of the chromatin, with the most condensed regions of chromatin typically beginning their replication last. After the replication fork has passed, chromatin structure is re-formed by the addition of new histones to the old histones that are directly inherited by each daughter DNA molecule.
Cell_Biology_Alberts_1240	Cell_Biology_Alberts	Eukaryotes solve the problem of replicating the ends of their linear chromosomes with a specialized end structure, the telomere, maintained by a special nucleotide polymerizing enzyme called telomerase. Telomerase extends one of the DNA strands at the end of a chromosome by using an RNA template that is an integral part of the enzyme itself, producing a highly repeated DNA sequence that typically extends for thousands of nucleotide pairs at each chromosome end. Telomeres have specialized structures that distinguish them from broken ends of chromosomes, ensuring that they are not mistakenly repaired.	Cell_Biology_Alberts. Eukaryotes solve the problem of replicating the ends of their linear chromosomes with a specialized end structure, the telomere, maintained by a special nucleotide polymerizing enzyme called telomerase. Telomerase extends one of the DNA strands at the end of a chromosome by using an RNA template that is an integral part of the enzyme itself, producing a highly repeated DNA sequence that typically extends for thousands of nucleotide pairs at each chromosome end. Telomeres have specialized structures that distinguish them from broken ends of chromosomes, ensuring that they are not mistakenly repaired.
Cell_Biology_Alberts_1241	Cell_Biology_Alberts	Maintaining the genetic stability that an organism needs for its survival requires not only an extremely accurate mechanism for replicating DNA, but also mechanisms for repairing the many accidental lesions that DNA continually suffers. Most such spontaneous changes in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair. Of the tens of thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few (less than 0.02%) accumulate as permanent mutations in the DNA sequence. The rest are eliminated with remarkable efficiency by DNA repair.	Cell_Biology_Alberts. Maintaining the genetic stability that an organism needs for its survival requires not only an extremely accurate mechanism for replicating DNA, but also mechanisms for repairing the many accidental lesions that DNA continually suffers. Most such spontaneous changes in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair. Of the tens of thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few (less than 0.02%) accumulate as permanent mutations in the DNA sequence. The rest are eliminated with remarkable efficiency by DNA repair.
Cell_Biology_Alberts_1242	Cell_Biology_Alberts	The importance of DNA repair is evident from the large investment that cells make in the enzymes that carry it out: several percent of the coding capacity of most genomes is devoted solely to DNA repair functions. The importance of DNA repair is also demonstrated by the increased rate of mutation that follows the inactivation of a DNA repair gene. Many DNA repair proteins and the genes that encode them—which we now know operate in a wide range of organisms, including humans—were originally identified in bacteria by the isolation and characterization of mutants that displayed an increased mutation rate or an increased sensitivity to DNA-damaging agents.	Cell_Biology_Alberts. The importance of DNA repair is evident from the large investment that cells make in the enzymes that carry it out: several percent of the coding capacity of most genomes is devoted solely to DNA repair functions. The importance of DNA repair is also demonstrated by the increased rate of mutation that follows the inactivation of a DNA repair gene. Many DNA repair proteins and the genes that encode them—which we now know operate in a wide range of organisms, including humans—were originally identified in bacteria by the isolation and characterization of mutants that displayed an increased mutation rate or an increased sensitivity to DNA-damaging agents.
Cell_Biology_Alberts_1243	Cell_Biology_Alberts	Recent studies of the consequences of a diminished capacity for DNA repair in humans have linked many human diseases with decreased repair (Table 5–2). Thus, we saw previously that defects in a human gene whose product normally functions to repair the mismatched base pairs resulting from DNA replication errors can lead to an inherited predisposition to cancers of the colon and some other organs, reflecting an increased mutation rate. In another human disease, xeroderma pigmentosum (XP), the afflicted individuals have an extreme sensitivity to ultraviolet radiation because they are unable to repair certain DNA photo-products. This repair defect results in an increased mutation rate that leads to serious skin lesions and an increased susceptibility to skin cancers. Finally, mutations in the Brca1 and Brca2 genes compromise a type of DNA repair known as homologous recombination and are a cause of hereditary breast and ovarian cancer.	Cell_Biology_Alberts. Recent studies of the consequences of a diminished capacity for DNA repair in humans have linked many human diseases with decreased repair (Table 5–2). Thus, we saw previously that defects in a human gene whose product normally functions to repair the mismatched base pairs resulting from DNA replication errors can lead to an inherited predisposition to cancers of the colon and some other organs, reflecting an increased mutation rate. In another human disease, xeroderma pigmentosum (XP), the afflicted individuals have an extreme sensitivity to ultraviolet radiation because they are unable to repair certain DNA photo-products. This repair defect results in an increased mutation rate that leads to serious skin lesions and an increased susceptibility to skin cancers. Finally, mutations in the Brca1 and Brca2 genes compromise a type of DNA repair known as homologous recombination and are a cause of hereditary breast and ovarian cancer.
Cell_Biology_Alberts_1244	Cell_Biology_Alberts	Without DNA Repair, Spontaneous DNA Damage Would Rapidly Change DNA Sequences Although DNA is a highly stable material—as required for the storage of genetic information—it is a complex organic molecule that is susceptible, even under normal cell conditions, to spontaneous changes that would lead to mutations if left unrepaired (Figure 5–37 and see Table 5–3). For example, the DNA of each Figure 5–37 A summary of spontaneous alterations that require DNA repair.	Cell_Biology_Alberts. Without DNA Repair, Spontaneous DNA Damage Would Rapidly Change DNA Sequences Although DNA is a highly stable material—as required for the storage of genetic information—it is a complex organic molecule that is susceptible, even under normal cell conditions, to spontaneous changes that would lead to mutations if left unrepaired (Figure 5–37 and see Table 5–3). For example, the DNA of each Figure 5–37 A summary of spontaneous alterations that require DNA repair.
Cell_Biology_Alberts_1245	Cell_Biology_Alberts	The sites on each nucleotide modified by spontaneous oxidative damage (red arrows), hydrolytic attack (blue arrows), and methylation (green arrows) are shown, with the width of each arrow indicating the relative frequency of each event (see Table 5–3). (After T. Lindahl, Nature 362:709–715, 1993. With permission from Macmillan Publishers Ltd.) human cell loses about 18,000 purine bases (adenine and guanine) every day because their N-glycosyl linkages to deoxyribose hydrolyze, a spontaneous reaction called depurination. Similarly, a spontaneous deamination of cytosine to uracil in DNA occurs at a rate of about 100 bases per cell per day (Figure 5–38). DNA bases are also occasionally damaged by an encounter with reactive metabolites produced in the cell, including reactive forms of oxygen and the high-energy methyl donor S-adenosylmethionine, or by exposure to chemicals in the environment. Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent	Cell_Biology_Alberts. The sites on each nucleotide modified by spontaneous oxidative damage (red arrows), hydrolytic attack (blue arrows), and methylation (green arrows) are shown, with the width of each arrow indicating the relative frequency of each event (see Table 5–3). (After T. Lindahl, Nature 362:709–715, 1993. With permission from Macmillan Publishers Ltd.) human cell loses about 18,000 purine bases (adenine and guanine) every day because their N-glycosyl linkages to deoxyribose hydrolyze, a spontaneous reaction called depurination. Similarly, a spontaneous deamination of cytosine to uracil in DNA occurs at a rate of about 100 bases per cell per day (Figure 5–38). DNA bases are also occasionally damaged by an encounter with reactive metabolites produced in the cell, including reactive forms of oxygen and the high-energy methyl donor S-adenosylmethionine, or by exposure to chemicals in the environment. Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent
Cell_Biology_Alberts_1246	Cell_Biology_Alberts	and the high-energy methyl donor S-adenosylmethionine, or by exposure to chemicals in the environment. Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form, for example, thymine dimers (Figure 5–39). If left uncorrected when the DNA is replicated, most of these changes would be expected to lead either to the deletion of one or more base pairs or to a base-pair substitution in the daughter DNA chain (Figure 5–40). The mutations would then be propagated throughout subsequent cell generations. Such a high rate of random changes in the DNA sequence would have disastrous consequences.	Cell_Biology_Alberts. and the high-energy methyl donor S-adenosylmethionine, or by exposure to chemicals in the environment. Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form, for example, thymine dimers (Figure 5–39). If left uncorrected when the DNA is replicated, most of these changes would be expected to lead either to the deletion of one or more base pairs or to a base-pair substitution in the daughter DNA chain (Figure 5–40). The mutations would then be propagated throughout subsequent cell generations. Such a high rate of random changes in the DNA sequence would have disastrous consequences.
Cell_Biology_Alberts_1247	Cell_Biology_Alberts	The DNA Double Helix Is Readily Repaired The double-helical structure of DNA is ideally suited for repair because it carries two separate copies of all the genetic information—one in each of its two strands. Thus, when one strand is damaged, the complementary strand retains an intact copy of the same information, and this copy is generally used to restore the correct nucleotide sequences to the damaged strand.	Cell_Biology_Alberts. The DNA Double Helix Is Readily Repaired The double-helical structure of DNA is ideally suited for repair because it carries two separate copies of all the genetic information—one in each of its two strands. Thus, when one strand is damaged, the complementary strand retains an intact copy of the same information, and this copy is generally used to restore the correct nucleotide sequences to the damaged strand.
Cell_Biology_Alberts_1248	Cell_Biology_Alberts	An indication of the importance of a double-strand helix to the safe storage of genetic information is that all cells use it; only a few small viruses use single-strand DNA or RNA as their genetic material. The types of repair processes described in this section cannot operate on such nucleic acids, and once damaged, the chance of a permanent nucleotide change occurring in these single-strand genomes of viruses is thus very high. It seems that only organisms with tiny genomes (and therefore tiny targets for DNA damage) can afford to encode their genetic information in any molecule other than a DNA double helix.	Cell_Biology_Alberts. An indication of the importance of a double-strand helix to the safe storage of genetic information is that all cells use it; only a few small viruses use single-strand DNA or RNA as their genetic material. The types of repair processes described in this section cannot operate on such nucleic acids, and once damaged, the chance of a permanent nucleotide change occurring in these single-strand genomes of viruses is thus very high. It seems that only organisms with tiny genomes (and therefore tiny targets for DNA damage) can afford to encode their genetic information in any molecule other than a DNA double helix.
Cell_Biology_Alberts_1249	Cell_Biology_Alberts	Figure 5–38 Depurination and deamination. These reactions are two of the most frequent spontaneous chemical reactions that create serious DNA damage in cells. Depurination can release guanine (shown here), as well as adenine, from DNA. The major type of deamination reaction converts cytosine to an altered DNA base, uracil (shown here), but deamination occurs on other bases as well. These reactions normally take place in double-helical DNA; for convenience, only one strand is shown. Figure 5–39 The most common type of thymine dimer. This type of damage occurs in the DNA of cells exposed to ultraviolet irradiation (as in sunlight). A similar dimer will form between any two neighboring pyrimidine bases (C or T residues) in DNA.	Cell_Biology_Alberts. Figure 5–38 Depurination and deamination. These reactions are two of the most frequent spontaneous chemical reactions that create serious DNA damage in cells. Depurination can release guanine (shown here), as well as adenine, from DNA. The major type of deamination reaction converts cytosine to an altered DNA base, uracil (shown here), but deamination occurs on other bases as well. These reactions normally take place in double-helical DNA; for convenience, only one strand is shown. Figure 5–39 The most common type of thymine dimer. This type of damage occurs in the DNA of cells exposed to ultraviolet irradiation (as in sunlight). A similar dimer will form between any two neighboring pyrimidine bases (C or T residues) in DNA.