Abstract
The rate of mutations in each site of a eukaryotic genome depends on a plethora of factors: nucleotides pools, asymmetry and timing of replication , types of DNA damage and parameters of its repair , translesion DNA synthesis and structure of chromatin. Studies of mutation mechanisms, traditionally performed with model systems, are currently boosted by revolutionary analysis of mutation landscapes of cancer genomes. Etiology of familial and sporadic cancers is connected to mutations in DNA polymerase and mismatch repair genes that unevenly lower the accuracy of replication in different chromosomal regions. Transient appearance of single-stranded DNA makes some genomic sites vulnerable to spontaneous or enzymatic deamination by AID/APOBECs that lead to clustered mutations called kataegis. Of special significance is an impact of cell ploidy on mutagenesis outcomes. Haploid cells with the highest levels of mutagenesis die due to lethal mutations. Descendants of hypermutable cells in diploids, where lethal recessive mutations load is tolerated, could be recovered and analyzed, permitting a glimpse into hitherto hidden mechanisms of mutagenesis.
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References
Abdulovic AL, Hile SE, Kunkel TA, Eckert KA (2011) The in vitro fidelity of yeast DNA polymerase delta and polymerase epsilon holoenzymes during dinucleotide microsatellite DNA synthesis. DNA Repair 10(5):497–505
Abolhassani N, Iyama T, Tsuchimoto D, Sakumi K et al (2010) NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals. Nucleic Acids Res 38(9):2891–2903
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA et al (2013) Signatures of mutational processes in human cancer. Nature 500(7463):415–421
Ames BN, Gold LS (1991) Endogenous mutagens and the causes of aging and cancer. Mutat Res 250(1–2):3–16
Araki H (2011) Initiation of chromosomal DNA replication in eukaryotic cells; contribution of yeast genetics to the elucidation. Genes Genet Syst 86(3):141–149
Behmanesh M, Sakumi K, Abolhassani N, Toyokuni S et al (2009) ITPase-deficient mice show growth retardation and die before weaning. Cell Death Differ 16(10):1315–1322
Budke B, Kuzminov A (2009) Production of clastogenic DNA precursors by the nucleotide metabolism in Escherichia coli. Mol Microbiol 75(1):230–245
Burns MB, Lackey L, Carpenter MA, Rathore A et al (2013) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494(7437):366–370
Cescon DW, Haibe-Kains B, Mak TW (2015) APOBEC3B expression in breast cancer reflects cellular proliferation, while a deletion polymorphism is associated with immune activation. Proc Natl Acad Sci USA 112(9):2841–2846
Chan K, Roberts SA, Klimczak LJ, Sterling JF et al (2015) An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers. Nat Genet 47(9):1067–1072
Cleary JD, Pearson CE (2005) Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability. Trends Genet 21(5):272–280
Colussi C, Parlanti E, Degan P, Aquilina G et al (2002) The mammalian mismatch repair pathway removes DNA 8-oxodGMP incorporated from the oxidized dNTP pool. Curr Biol 12(11):912–918
Conticello SG (2012) Creative deaminases, self-inflicted damage, and genome evolution. Ann NY Acad Sci 1267:79–85
D’Errico M, Parlanti E, Dogliotti E (2008) Mechanism of oxidative DNA damage repair and relevance to human pathology. Mutat Res 659(1–2):4–14
De Luca G, Russo MT, Degan P, Tiveron C et al (2008) A role for oxidized DNA precursors in Huntington’s disease-like striatal neurodegeneration. PLoS Genet 4(11):e1000266
Dedon PC, Tannenbaum SR (2004) Reactive nitrogen species in the chemical biology of inflammation. Arch Biochem Biophys 423(1):12–22
Deem A, Keszthelyi A, Blackgrove T, Vayl A et al (2011) Break-induced replication is highly inaccurate. PLoS Biol 9(2):e1000594
Di Noia JM, Neuberger MS (2004) Immunoglobulin gene conversion in chicken DT40 cells largely proceeds through an abasic site intermediate generated by excision of the uracil produced by AID-mediated deoxycytidine deamination. Eur J Immunol 34(2):504–508
Drake JW (1999) The distribution of rates of spontaneous mutation over viruses, prokaryotes, and eukaryotes. Ann NY Acad Sci 870:100–107
Fijalkowska IJ, Jonczyk P, Tkaczyk MM, Bialoskorska M et al (1998) Unequal fidelity of leading strand and lagging strand DNA replication on the Escherichia coli chromosome. Proc Natl Acad Sci USA 95(17):10020–10025
Fortune JM, Pavlov YI, Welch CM, Johansson E et al (2005) Saccharomyces cerevisiae DNA polymerase delta: high fidelity for base substitutions but lower fidelity for single- and multi-base deletions. J Biol Chem 280(33):29980–29987
Franchini DM, Petersen-Mahrt SK (2014) AID and APOBEC deaminases: balancing DNA damage in epigenetics and immunity. Epigenomics 6(4):427–443
Gad H, Koolmeister T, Jemth AS, Eshtad S et al (2014) MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 508(7495):215–221
Gan GN, Wittschieben JP, Wittschieben BO, Wood RD (2008) DNA polymerase zeta (pol zeta) in higher eukaryotes. Cell Res 18(1):174–183
Garg P, Burgers PM (2005) DNA polymerases that propagate the eukaryotic DNA replication fork. Crit Rev Biochem Mol Biol 40(2):115–128
Garg P, Stith CM, Sabouri N, Johansson E et al (2004) Idling by DNA polymerase d maintains a ligatable nick during lagging-strand DNA replication. Genes Dev 18(22):2764–2773
Gordenin DA, Inge-Vechtomov SG (1981) Mechanism of mutant induction in the ade2 gene of diploid Saccharomyces cerevisiae yeasts by ultraviolet rays. Genetika 17(5):822–831
Gordenin DA, Resnick MA (1998) Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability. Mutat Res 400(1–2):45–58
Gutierrez PJ, Wang TS (2003) Genomic instability induced by mutations in Saccharomyces cerevisiae POL1. Genetics 165(1):65–81
Hanawalt PC (2007) Paradigms for the three Rs: DNA replication, recombination, and repair. Mol Cell 28(5):702–707
Herr AJ, Ogawa M, Lawrence NA, Williams LN et al (2011) Mutator suppression and escape from replication error-induced extinction in yeast. PLoS Genet 7(10):e1002282
Hicks WM, Kim M, Haber JE (2010) Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329(5987):82–85
Hirano M (2015) Evolution of vertebrate adaptive immunity: immune cells and tissues, and AID/APOBEC cytidine deaminases. BioEssays 37(8):877–887
Hirota K, Yoshikiyo K, Guilbaud G, Tsurimoto T et al (2015) The POLD3 subunit of DNA polymerase delta can promote translesion synthesis independently of DNA polymerase zeta. Nucleic Acids Res 43(3):1671–1683
Hochhauser SJ, Weiss B (1978) Escherichia coli mutants deficient in deoxyuridine triphosphatase. J Bacteriol 134(1):157–166
Holbeck SL, Strathern JN (1997) A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147(3):1017–1024
Honjo T, Nagaoka H, Shinkura R, Muramatsu M (2005) AID to overcome the limitations of genomic information. Nat Immunol 6(7):655–661
Iwaki T, Kawamura A, Ishino Y, Kohno K et al (1996) Preferential replication-dependent mutagenesis in the lagging DNA strand in Escherichia coli. Mol Gen Genet 251(6):657–664
Jin YH, Garg P, Stith CM, Al-Refai H et al (2005) The multiple biological roles of the 3’→5’ exonuclease of Saccharomyces cerevisiae DNA polymerase δ require switching between the polymerase and exonuclease domains. Mol Cell Biol 25(1):461–471
Johansson E, Macneill SA (2010) The eukaryotic replicative DNA polymerases take shape. Trends Biochem Sci 35(6):339–347
Johnson RE, Klassen R, Prakash L, Prakash S (2015) A major role of DNA polymerase delta in replication of both the leading and lagging DNA strands. Mol Cell 59(2):163–175
Kadyrova LY, Blanko ER, Kadyrov FA (2011) CAF-I-dependent control of degradation of the discontinuous strands during mismatch repair. Proc Natl Acad Sci USA 108(7):2753–2758
Karthikeyan R, Vonarx EJ, Straffon AF, Simon M et al (2000) Evidence from mutational specificity studies that yeast DNA polymerases delta and epsilon replicate different DNA strands at an intracellular replication fork. J Mol Biol 299(2):405–419
Kato L, Stanlie A, Begum NA, Kobayashi M et al (2012) An evolutionary view of the mechanism for immune and genome diversity. Journal of Immunology 188(8):3559–3566 (Baltimore)
Kazanov MD, Roberts SA, Polak P, Stamatoyannopoulos J et al (2015) APOBEC-induced cancer mutations are uniquely enriched in early-replicating, gene-dense, and active chromatin regions. Cell Rep 13(6):1103–1109
Kesti T, Flick K, Keranen S, Syvaoja JE et al (1999) DNA polymerase ε catalytic domains are dispensable for DNA replication, DNA repair, and cell viability. Mol Cell 3(5):679–685
Kochenova OV, Daee DL, Mertz TM, Shcherbakova PV (2015) DNA polymerase zeta-dependent lesion bypass in Saccharomyces cerevisiae is accompanied by error-prone copying of long stretches of adjacent DNA. PLoS Genet 11(3):e1005110
Korona DA, Lecompte KG, Pursell ZF (2011) The high fidelity and unique error signature of human DNA polymerase epsilon. Nucleic Acids Res 39(5):1763–1773
Kovtun IV, McMurray CT (2001) Trinucleotide expansion in haploid germ cells by gap repair. Nat Genet 27(4):407–411
Kovtun IV, Liu Y, Bjoras M, Klungland A et al (2007) OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447(7143):447–452
Kozmin SG, Schaaper RM, Shcherbakova PV, Kulikov VN et al (1998) Multiple antimutagenesis mechanisms affect mutagenic activity and specificity of the base analog 6-N-hydroxylaminopurine in bacteria and yeast. Mutat Res 402(1–2):41–50
Kozmin SG, Leroy P, Pavlov YI, Schaaper RM (2008) YcbX and yiiM, two novel determinants for resistance of E. coli to N-hydroxylated base analogues. Mol Microbiol 68(1):51–65
Kulikov VV, Derkatch IL, Noskov VN, Tarunina OV et al (2001) Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the LYS2 gene of yeast Saccharomyces cerevisiae. Mutat Res 473(2):151–161
Kumar D, Abdulovic AL, Viberg J, Nilsson AK et al (2011) Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools. Nucleic Acids Res 39(4):1360–1371
Kunkel TA (2004) DNA replication fidelity. J Biol Chem 279(17):16895–16898
Kunkel TA, Erie DA (2005) DNA mismatch repair. Annu Rev Biochem 74:681–710
Kunkel TA, Burgers PM (2008) Dividing the workload at a eukaryotic replication fork. Trends Cell Biol 18(11):521–527
Lada AG, Frahm Krick C, Kozmin SG, Mayorov VI et al (2011a) Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast. Biochemistry 76:131–146 (Moscow)
Lada AG, Waisertreiger IS, Grabow CE, Prakash A et al (2011b) Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA. PLoS ONE 6(9):e24848
Lada AG, Dhar A, Boissy RJ, Hirano M et al (2012) AID/APOBEC cytosine deaminase induces genome-wide kataegis. Biol Direct 7:47
Lada AG, Stepchenkova EI, Waisertreiger IS, Noskov VN et al (2013) Genome-wide mutation avalanches induced in diploid yeast cells by a base analog or an APOBEC deaminase. PLoS Genet 9(9):e1003736
Lada AG, Kliver SF, Dhar A, Polev DE et al (2015) Disruption of transcriptional coactivator Sub1 leads to genome-wide re-distribution of clustered mutations induced by APOBEC in active yeast genes. PLoS Genet 11(5):e1005217
Lahue RS, Slater DL (2003) DNA repair and trinucleotide repeat instability. Front Biosci 8:s653–s665
Lang GI, Murray AW (2011) Mutation rates across budding yeast chromosome VI are correlated with replication timing. Genome Biol Evol 3:799–811
Larrea AA, Lujan SA, Nick McElhinny SA, Mieczkowski PA et al (2010) Genome-wide model for the normal eukaryotic DNA replication fork. Proc Natl Acad Sci USA 107(41):17674–17679
Lawrence MS, Stojanov P, Polak P, Kryukov GV et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499(7457):214–218
Liu L, De S, Michor F (2013) DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes. Nat Commun 4:1502
Liu S, Lu G, Ali S, Liu W et al (2015) Okazaki fragment maturation involves alpha-segment error editing by the mammalian FEN1/MutSalpha functional complex. EMBO J 34(13):1829–1843
Lujan SA, Clausen AR, Clark AB, MacAlpine HK et al (2014) Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition. Genome Res 24(11):1751–1764
Lynch M (2010) Evolution of the mutation rate. Trends Genet 26(8):345–352
Magni GE, von Borstel RC (1962) Different rates of spontaneous mutation during mitosis and meiosis in yeast. Genetics 47:1097–1108
Makarova AV, Burgers PM (2015) Eukaryotic DNA polymerase zeta. DNA Repair 29:47–55
Maki H, Sekiguchi M (1992) MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature 355(6357):273–275
Malkova A, Ira G (2013) Break-induced replication: functions and molecular mechanism. Curr Opin Genet Dev 23(3):271–279
Mathews CK (2006) DNA precursor metabolism and genomic stability. FASEB J 20(9):1300–1314
Mathews CK, Ji J (1992) DNA precursor asymmetries, replication fidelity, and variable genome evolution. BioEssays 14(5):295–301
Mertz TM, Sharma S, Chabes A, Shcherbakova PV (2015) Colon cancer-associated mutator DNA polymerase delta variant causes expansion of dNTP pools increasing its own infidelity. Proc Natl Acad Sci USA 112(19):E2467–E2476
Michaels ML, Miller JH (1992) The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol 174(20):6321–6325
Miller JH (1996) The relevance of bacterial mutators to understanding human cancer. Cancer Surv 28:141–153
Mirkin SM (2006) DNA structures, repeat expansions and human hereditary disorders. Curr Opin Struct Biol 16(3):351–358
Miyabe I, Kunkel TA, Carr AM (2011) The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet 7(12):e1002407
Miyabe I, Mizuno K, Keszthelyi A, Daigaku Y et al (2015) Polymerase delta replicates both strands after homologous recombination-dependent fork restart. Nat Struct Mol Biol 22(11):932–938. doi:10.1038/nsmb.3100
Morrison A, Sugino A (1994) The 3’→ 5’ exonucleases of both DNA polymerases delta and epsilon participate in correcting errors of DNA replication in Saccharomyces cerevisiae. Mol Gen Genet 242(3):289–296
Morrison A, Araki H, Clark AB, Hamatake RK et al (1990) A third essential DNA polymerase in S. cerevisiae. Cell 62(6):1143–1151
Muramatsu M, Kinoshita K, Fagarasan S, Yamada S et al (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102(5):553–563
Neuberger MS, Rada C (2007) Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase eta for A/T. J Exp Med 204(1):7–10
Neuberger MS, Harris RS, Di Noia J, Petersen-Mahrt SK (2003) Immunity through DNA deamination. Trends Biochem Sci 28(6):305–312
Nick McElhinny SA, Gordenin DA, Stith CM, Burgers PM et al (2008) Division of labor at the eukaryotic replication fork. Mol Cell 30(2):137–144
Nick McElhinny SA, Kumar D, Clark AB, Watt DL et al (2010) Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol 6(10):774–781
Niimi A, Limsirichaikul S, Yoshida S, Iwai S et al (2004) Palm mutants in DNA polymerases α and η alter DNA replication fidelity and translesion activity. Mol Cell Biol 24(7):2734–2746
Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P et al (2012) Mutational processes molding the genomes of 21 breast cancers. Cell 149(5):979–993
Northam MR, Garg P, Baitin DM, Burgers PM et al (2006) A novel function of DNA polymerase zeta regulated by PCNA. EMBO J 25(18):4316–4325
Northam MR, Robinson HA, Kochenova OV, Shcherbakova PV (2010) Participation of DNA polymerase zeta in replication of undamaged DNA in S. cerevisiae. Genetics 184(1):27–42
Ohya T, Kawasaki Y, Hiraga S, Kanbara S et al (2002) The DNA polymerase domain of pol(e) is required for rapid, efficient, and highly accurate chromosomal DNA replication, telomere length maintenance, and normal cell senescence in Saccharomyces cerevisiae. J Biol Chem 277(31):28099–28108
Pang B, McFaline JL, Burgis NE, Dong M et al (2012) Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA. Proc Natl Acad Sci USA 109(7):2319–2324
Pavlov II, Noskov VN, Chernov Iu O, Gordenin DA (1988) Mutability of LYS2 gene in diploid Saccharomyces yeasts. II. Frequency of mutants induced by 6-N-hydroxylaminopurine and propiolactone. Genetika 24(10):1752–1760
Pavlov YI, Shcherbakova PV (2010) DNA polymerases at the eukaryotic fork-20 years later. Mutat Res 685(1–2):45–53
Pavlov YI, Noskov VN, Lange EK, Moiseeva EV et al (1991) The genetic activity of N6-hydroxyadenine and 2-amino-N6-hydroxyadenine in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae. Mutat Res 253(1):33–46
Pavlov YI, Shcherbakova PV, Kunkel TA (2001) In vivo consequences of putative active site missense mutations in yeast replicative DNA polymerases α, ε, δ and ζ. Genetics 159(1):47–64
Pavlov YI, Newlon CS, Kunkel TA (2002a) Yeast origins establish a strand bias for replicational mutagenesis. Mol Cell 10(1):207–213
Pavlov YI, Rogozin IB, Galkin AP, Aksenova AY et al (2002b) Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin k light chain transgene. Proc Natl Acad Sci USA 99(15):9954–9959
Pavlov YI, Mian IM, Kunkel TA (2003) Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. Curr Biol 13(9):744–748
Pavlov YI, Maki S, Maki H, Kunkel TA (2004) Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations. BMC Biol 2(1):11
Pavlov YI, Frahm C, McElhinny SA, Niimi A et al (2006a) Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta. Curr Biol 16(2):202–207
Pavlov YI, Shcherbakova PV, Rogozin IB (2006b) Roles of DNA polymerases in replication, repair, and recombination in eukaryotes. Int Rev Cytol 255:41–132
Pearson CE, Edamura KN, Cleary JD (2005) Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 6(10):729–742
Pellegrini L (2012) The Pol alpha-primase complex. Sub-cell Biochem 62:157–169
Petersen-Mahrt SK, Neuberger MS (2003) In vitro deamination of cytosine to uracil in single-stranded DNA by apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). J Biol Chem 278(22):19583–19586
Petersen-Mahrt SK, Harris RS, Neuberger MS (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418(6893):99–103
Pham P, Bransteitter R, Petruska J, Goodman MF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424(6944):103–107
Pham P, Smolka MB, Calabrese P, Landolph A et al (2008) Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase. J Biol Chem 283(25):17428–17439
Poltoratsky VP, Wilson SH, Kunkel TA, Pavlov YI (2004) Recombinogenic phenotype of human activation-induced cytosine deaminase. J Immunol 172(7):4308–4313
Poltoratsky V, Heacock M, Kissling GE, Prasad R et al (2010) Mutagenesis dependent upon the combination of activation-induced deaminase expression and a double-strand break. Mol Immunol 48(1–3):164–170
Prakash S, Johnson RE, Prakash L (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem 74:317–353
Pursell ZF, Isoz I, Lundstrom EB, Johansson E et al (2007) Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 317(5834):127–130
Rattray AJ, Shafer BK, McGill CB, Strathern JN (2002) The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of S. cerevisiae. Genetics 162(3):1063–1077
Refsland EW, Harris RS (2013) The APOBEC3 family of retroelement restriction factors. Curr Top Microbiol Immunol 371:1–27
Reijns MA, Rabe B, Rigby RE, Mill P et al (2012) Enzymatic removal of ribonucleotides from DNA is essential for Mammalian genome integrity and development. Cell 149(5):1008–1022
Reijns MA, Kemp H, Ding J, de Proce SM et al (2015) Lagging-strand replication shapes the mutational landscape of the genome. Nature 518(7540):502–506
Roberts SA, Gordenin DA (2014) Hypermutation in human cancer genomes: footprints and mechanisms. Nat Rev Cancer 14(12):786–800
Roberts JD, Izuta S, Thomas DC, Kunkel TA (1994) Mispair-, site-, and strand-specific error rates during simian virus 40 origin-dependent replication in vitro with excess deoxythymidine triphosphate. J Biol Chem 269(3):1711–1717
Roberts SA, Sterling J, Thompson C, Harris S et al (2012) Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell 46(4):424–435
Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA et al (2013) An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45(9):970–976
Rogozin IB, Pavlov YI, Bebenek K, Matsuda T et al (2001) Somatic mutation hotspots correlate with DNA polymerase eta error spectrum. Nat Immunol 2(6):530–536. doi:10.1038/88732
Rogozin IB, Iyer LM, Liang L, Glazko GV et al (2007) Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nat Immunol 8(6):647–656
Rumbaugh JA, Henricksen LA, DeMott MS, Bambara RA (1999) Cleavage of substrates with mismatched nucleotides by Flap endonuclease-1. Implications for mammalian Okazaki fragment processing. J Biol Chem 274(21):14602–14608
Saini N, Ramakrishnan S, Elango R, Ayyar S et al (2013a) Migrating bubble during break-induced replication drives conservative DNA synthesis. Nature 502(7471):389–392
Saini N, Zhang Y, Nishida Y, Sheng Z et al (2013b) Fragile DNA motifs trigger mutagenesis at distant chromosomal loci in Saccharomyces cerevisiae. PLoS Genet 9(6):e1003551
Sakofsky CJ, Roberts SA, Malc E, Mieczkowski PA et al (2014) Break-induced replication is a source of mutation clusters underlying kataegis. Cell Rep 7(5):1640–1648
Sakumi K, Abolhassani N, Behmanesh M, Iyama T et al (2010) ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells. Mutat Res 703(1):43–50
Sale JE (2013) Translesion DNA synthesis and mutagenesis in eukaryotes. Cold Spring Harb Perspect Biol 5(3):a012708
Salk JJ, Fox EJ, Loeb LA (2010) Mutational heterogeneity in human cancers: origin and consequences. Annu Rev Pathol 5:51–75
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85
Schmitz KM, Petersen-Mahrt SK (2012) AIDing the immune system-DIAbolic in cancer. Semin Immunol 24(4):241–245
Schopf B, Bregenhorn S, Quivy JP, Kadyrov FA et al (2012) Interplay between mismatch repair and chromatin assembly. Proc Natl Acad Sci USA 109(6):1895–1900
Sekiguchi M, Tsuzuki T (2002) Oxidative nucleotide damage: consequences and prevention. Oncogene 21(58):8895–8904
Shah KA, Shishkin AA, Voineagu I, Pavlov YI et al (2012) Role of DNA polymerases in repeat-mediated genome instability. Cell Rep 2(5):1088–1095
Shcherbakova PV, Pavlov YI (1993) Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the URA3 gene of the yeast S. cerevisiae. Mutagenesis 8(5):417–421
Shcherbakova PV, Pavlov YI (1996) 3’→5’ exonucleases of DNA polymerases epsilon and delta correct base analog induced DNA replication errors on opposite DNA strands in Saccharomyces cerevisiae. Genetics 142(3):717–726
Shcherbakova PV, Pavlov YI, Chilkova O, Rogozin IB et al (2003) Unique error signature of the four-subunit yeast DNA polymerase epsilon. J Biol Chem 278(44):43770–43780
Shendure J, Akey JM (2015) The origins, determinants, and consequences of human mutations. Science 349(6255):1478–1483
Shishkin AA, Voineagu I, Matera R, Cherng N et al (2009) Large-scale expansions of Friedreich’s ataxia GAA repeats in yeast. Mol Cell 35(1):82–92
Simandan T, Sun J, Dix TA (1998) Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl radicals. Biochem J 335(Pt 2):233–240
Smith DJ, Whitehouse I (2012) Intrinsic coupling of lagging-strand synthesis to chromatin assembly. Nature 483(7390):434–438
Stillman B (2015) Reconsidering DNA polymerases at the replication fork in eukaryotes. Mol Cell 59(2):139–141
Storb U (2014) Why does somatic hypermutation by AID require transcription of its target genes? Adv Immunol 122:253–277
Strathern JN, Shafer BK, McGill CB (1995) DNA synthesis errors associated with double-strand-break repair. Genetics 140(3):965–972
Supek F, Lehner B (2015) Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 521(7550):81–84
Tahirov TH (2012) Structure and function of eukaryotic DNA polymerase delta. Subcell Biochem 63:217–236
Tanaka S, Cao K, Niimi A, Limsirichaikul S et al (2010) Functions of base selection step in human DNA polymerase alpha. DNA Repair 9(5):534–541
Tang W, Dominska M, Gawel M, Greenwell PW et al (2013) Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich’s ataxia. DNA Repair 12(1):10–17
Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA et al (2013) DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife 2:e00534
Taylor BJ, Wu YL, Rada C (2014) Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes. Elife 3:e03553
Tran HT, Degtyareva NP, Gordenin DA, Resnick MA (1999) Genetic factors affecting the impact of DNA polymerase δ proofreading activity on mutation avoidance in yeast. Genetics 152(1):47–59
Vaisman A, Woodgate R (2015) Redundancy in ribonucleotide excision repair: Competition, compensation, and cooperation. DNA Repair 29:74–82
Veaute X, Fuchs RP (1993) Greater susceptibility to mutations in lagging strand of DNA replication in Escherichia coli than in leading strand. Science 261(5121):598–600
Waga S, Stillman B (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67:721–751
Wagner SD, Neuberger MS (1996) Somatic hypermutation of immunoglobulin genes. Annu Rev Immunol 14:441–457
Waisertreiger IS, Liston VG, Menezes MR, Kim HM et al (2012) Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools. Environ Mol Mutagen 53:699–734
Walker BA, Wardell CP, Murison A, Boyle EM et al (2015) APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma. Nat Commun 6:6997
Wang X, Ira G, Tercero JA, Holmes AM et al (2004) Role of DNA replication proteins in double-strand break-induced recombination in S. cerevisiae. Mol Cell Biol 24(16):6891–6899
Watt DL, Buckland RJ, Lujan SA, Kunkel TA et al (2015) Genome-wide analysis of the specificity and mechanisms of replication infidelity driven by imbalanced dNTP pools. Nucleic Acids Res 44:1669–1680
Wu PF, Chen YS, Kuo TY, Lin HH et al (2015) APOBEC3B: a potential factor suppressing growth of human hepatocellular carcinoma cells. Anticancer Res 35(3):1521–1527
Yang W, Woodgate R (2007) What a difference a decade makes: insights into translesion DNA synthesis. Proc Natl Acad Sci USA 104(40):15591–15598
Yeeles JT, Deegan TD, Janska A, Early A et al (2015) Regulated eukaryotic DNA replication origin firing with purified proteins. Nature 519(7544):431–435
Zeng X, Winter DB, Kasmer C, Kraemer KH et al (2001) DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nat Immunol 2(6):537–541
Zhong X, Garg P, Stith CM, Nick McElhinny SA et al (2006) The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteins. Nucleic Acids Res 34(17):4731–4742
Acknowledgments
We are thankful Dr. V.L. Korogodina and Dr. S.G. Inge-Vechtomov for the invitation to present the lecture that was a starting point of work on the current review at the IV International meeting dedicated to the 115th anniversary of the birth of N.W.Timofeeff-Ressovsky and his international scientific school in Saint-Petersburg. We are grateful to Dr. Erik Johansson and Dr. Peter Burgers for sharing preparations of yeast DNA pols. The work was supported by UNMC Eppley Institute Pilot grant in 2014–2015, grant RFBR # 15-04-08625 and Research Grant of SPbU #1.38.426.2015
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Pavlov, Y.I., Lada, A.G., Grabow, C., Stepchenkova, E.I. (2016). Mechanisms of Global and Region-Specific Control of Mutagenesis. In: Korogodina, V., Mothersill, C., Inge-Vechtomov, S., Seymour, C. (eds) Genetics, Evolution and Radiation. Springer, Cham. https://doi.org/10.1007/978-3-319-48838-7_6
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