A critical balance: DNTPs and the maintenance of genome stability

Genes

Volumn 8, Issue 2, 2017, Pages

  Pai, Chen Chun ^a   Kearsey, Stephen E ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

DNA polymerase; DNTP; Genome instability; Proofreading; Replication fidelity; Ribonucleotide reductase

Indexed keywords

CDC45 PROTEIN; CDC7 PROTEIN; CELL CYCLE PROTEIN 6; CYCLIN DEPENDENT KINASE; DBF4 PROTEIN; DEOXYCYTIDINE TRIPHOSPHATE; DEOXYGUANOSINE TRIPHOSPHATE; DNA DIRECTED DNA POLYMERASE EPSILON; GINS PROTEIN; MINICHROMOSOME MAINTENANCE PROTEIN 2; MINICHROMOSOME MAINTENANCE PROTEIN 2 7; MITOCHONDRIAL DNA; REPLICATION LICENSING FACTOR CDT1; RIBONUCLEOTIDE REDUCTASE; THYMIDINE TRIPHOSPHATE; UNCLASSIFIED DRUG;

CANCER CHEMOTHERAPY; CHROMOSOME; DNA REPAIR; DNA REPLICATION; DNA SYNTHESIS; ENZYME ACTIVATION; ENZYME INHIBITION; GENOMIC INSTABILITY; HUMAN; MISMATCH REPAIR; NONHUMAN; PROTEIN ASSEMBLY; PROTEIN DEGRADATION; PROTEIN DNA BINDING; PROTEIN PHOSPHORYLATION; REVIEW; SACCHAROMYCES CEREVISIAE;

EID: 85011320812     PISSN: None     EISSN: 20734425     Source Type: Journal    
DOI: 10.3390/genes8020057     Document Type: Review

References (138)

1. Skoneczna, A.; Kaniak, A.; Skoneczny, M. Genetic instability in budding and fission yeast-sources and mechanisms. FEMS Microbiol. Rev. 2015, 39, 917-967.
2. Carr, A.M.; Paek, A.L.; Weinert, T. DNA replication: Failures and inverted fusions. Semin. Cell Dev. Biol. 2011, 22, 866-874.
3. Gomez-Escoda, B.; Wu, P.Y. The programme of DNA replication: Beyond genome duplication. Biochem. Soc. Trans. 2013, 41, 1720-1725.
4. Recolin, B.; van der Laan, S.; Tsanov, N.; Maiorano, D. Molecular mechanisms of DNA replication checkpoint activation. Genes 2014, 5, 147-175.
5. Aguilera, A.; Gomez-Gonzalez, B. Genome instability: A mechanistic view of its causes and consequences. Nat. Rev. Genet. 2008, 9, 204-217.
6. Hastings, P.J.; Lupski, J.R.; Rosenberg, S.M.; Ira, G. Mechanisms of change in gene copy number. Nat. Rev. Genet. 2009, 10, 551-564.
7. Holland, A.J.; Cleveland, D.W. Boveri revisited: Chromosomal instability, aneuploidy and tumorigenesis. Nat. Rev. Mol. Cell Biol. 2009, 10, 478-487.
8. Magdalou, I.; Lopez, B.S.; Pasero, P.; Lambert, S.A. The causes of replication stress and their consequences on genome stability and cell fate. Semin. Cell Dev. Biol. 2014, 30, 154-164.
9. Hills, S.A.; Diffley, J.F. DNA replication and oncogene-induced replicative stress. Curr. Biol. 2014, 24, R435-R444.
10. Mathews, C.K. DNA precursor metabolism and genomic stability. FASEB J. 2006, 20, 1300-1314.
11. Mathews, C.K. Deoxyribonucleotide metabolism, mutagenesis and cancer. Nat. Rev. Cancer 2015, 15, 528-539.
12. Mathews, C.K. Deoxyribonucleotides as genetic and metabolic regulators. FASEB J. 2014, 28, 3832-3840.
13. Yeeles, J.T.; Deegan, T.D.; Janska, A.; Early, A.; Diffley, J.F. Regulated eukaryotic DNA replication origin firing with purified proteins. Nature 2015, 519, 431-435.
14. Siddiqui, K.; On, K.F.; Diffley, J.F. Regulating DNA replication in eukarya. Cold Spring Harb. Perspect. Biol. 2013, doi:10.1101/cshperspect.a012930.
15. Prioleau, M.N.; MacAlpine, D.M. DNA replication origins-where do we begin? Genes Dev. 2016, 30, 1683-1697.
16. Pursell, Z.F.; Isoz, I.; Lundstrom, E.B.; Johansson, E.; Kunkel, T.A. Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 2007, 317, 127-130.
17. Burgers, P.M.; Gordenin, D.; Kunkel, T.A. Who is leading the replication fork, pol epsilon or pol delta? Mol. Cell 2016, 61, 492-493.
18. Johnson, R.E.; Klassen, R.; Prakash, L.; Prakash, S. A major role of DNA polymerase delta in replication of both the leading and lagging DNA strands. Mol. Cell 2015, 59, 163-175.
19. Kohalmi, S.E.; Glattke, M.; McIntosh, E.M.; Kunz, B.A. Mutational specificity of DNA precursor pool imbalances in yeast arising from deoxycytidylate deaminase deficiency or treatment with thymidylate. J. Mol. Biol. 1991, 220, 933-946.
20. Reichard, P. Interactions between deoxyribonucleotide and DNA synthesis. Annu. Rev. Biochem 1988, 57, 349-374.
21. Hofer, A.; Crona, M.; Logan, D.T.; Sjoberg, B.M. DNA building blocks: Keeping control of manufacture. Crit. Rev. Biochem. Mol. Biol. 2012, 47, 50-63.
22. Nordlund, P.; Reichard, P. Ribonucleotide reductases. Annu. Rev. Biochem. 2006, 75, 681-706.
23. Niida, H.; Shimada, M.; Murakami, H.; Nakanishi, M. Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells. Cancer Sci. 2010, 101, 2505-2509.
24. Guarino, E.; Salguero, I.; Kearsey, S.E. Cellular regulation of ribonucleotide reductase in eukaryotes. Semin. Cell. Dev. Biol. 2014, 30, 97-103.
25. Fasullo, M.; Endres, L. Nucleotide salvage deficiencies, DNA damage and neurodegeneration. Int. J. Mol. Sci. 2015, 16, 9431-9449.
26. Goldstone, D.C.; Ennis-Adeniran, V.; Hedden, J.J.; Groom, H.C.; Rice, G.I.; Christodoulou, E.; Walker, P.A.; Kelly, G.; Haire, L.F.; Yap, M.W.; et al. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 2011, 480, 379-382.
27. Stillman, B. Deoxynucleoside triphosphate (dNTP) synthesis and destruction regulate the replication of both cell and virus genomes. Proc. Natl. Acad. Sci. USA 2013, 110, 14120-14121.
28. Rhind, N.; Gilbert, D.M. DNA replication timing. Cold Spring Harb. Perspect. Biol. 2013, doi:10.1101/cshperspect.a010132.
29. Ullman, B.; Clift, S.M.; Gudas, L.J.; Levinson, B.B.; Wormsted, M.A.; Martin, D.W., Jr. Alterations in deoxyribonucleotide metabolism in cultured cells with ribonucleotide reductase activities refractory to feedback inhibition by 2’-deoxyadenosine triphosphate. J. Biol. Chem. 1980, 255, 8308-8314.
30. Chabes, A.; Georgieva, B.; Domkin, V.; Zhao, X.; Rothstein, R.; Thelander, L. Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase. Cell 2003, 112, 391-401.
31. Liu, C.; Powell, K.A.; Mundt, K.; Wu, L.; Carr, A.M.; Caspari, T. Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms. Genes Dev. 2003, 17, 1130-1140.
32. Zhao, X.; Muller, E.G.; Rothstein, R. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol. Cell 1998, 2, 329-340.
33. Chabes, A.; Stillman, B. Constitutively high dntp concentration inhibits cell cycle progression and the DNA damage checkpoint in yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 2007, 104, 1183-1188.
34. Franzolin, E.; Pontarin, G.; Rampazzo, C.; Miazzi, C.; Ferraro, P.; Palumbo, E.; Reichard, P.; Bianchi, V. The deoxynucleotide triphosphohydrolase samhd1 is a major regulator of DNA precursor pools in mammalian cells. Proc. Natl. Acad. Sci. USA 2013, 110, 14272-14277.
35. Gon, S.; Napolitano, R.; Rocha, W.; Coulon, S.; Fuchs, R.P. Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli. Proc. Natl. Acad. Sci. USA 2011, 108, 19311-19316.
36. Moss, J.; Tinline-Purvis, H.; Walker, C.A.; Folkes, L.K.; Stratford, M.R.; Hayles, J.; Hoe, K.L.; Kim, D.U.; Park, H.O.; Kearsey, S.E.; et al. Break-induced ATR and Ddb1-Cul4(Cdt)2 ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. Genes Dev. 2010, 24, 2705-2716.
37. Davidson, M.B.; Katou, Y.; Keszthelyi, A.; Sing, T.L.; Xia, T.; Ou, J.; Vaisica, J.A.; Thevakumaran, N.; Marjavaara, L.; Myers, C.L.; et al. Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype. EMBO J. 2012, 31, 895-907.
38. Håkansson, P.; Hofer, A.; Thelander, L. Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. J. Biol. Chem. 2006, 281, 7834-7841.
39. Fleck, O.; Vejrup-Hansen, R.; Watson, A.; Carr, A.M.; Nielsen, O.; Holmberg, C. Spd1 accumulation causes genome instability independently of ribonucleotide reductase activity but functions to protect the genome when deoxynucleotide pools are elevated. J. Cell Sci. 2013, 126, 4985-4994.
40. Caras, I.W.; Martin, D.W., Jr. Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells. Mol. Cell Biol. 1988, 8, 2698-2704.
41. Weinberg, G.; Ullman, B.; Martin, D.W., Jr. Mutator phenotypes in mammalian cell mutants with distinct biochemical defects and abnormal deoxyribonucleoside triphosphate pools. Proc. Natl. Acad. Sci. USA 1981, 78, 2447-2451.
42. Beckman, R.A.; Loeb, L.A. Multi-stage proofreading in DNA replication. Q. Rev. Biophys. 1993, 26, 225-331.
43. Kunkel, T.A.; Bebenek, K. DNA replication fidelity. Annu. Rev. Biochem. 2000, 69, 497-529.
44. Prakash, S.; Prakash, L. Translesion DNA synthesis in eukaryotes: A one-or two-polymerase affair. Genes Dev. 2002, 16, 1872-1883.
45. Sabouri, N.; Viberg, J.; Goyal, D.K.; Johansson, E.; Chabes, A. Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage. Nucleic Acids Res. 2008, 36, 5660-5667.
46. Lis, E.T.; OʹNeill, B.M.; Gil-Lamaignere, C.; Chin, J.K.; Romesberg, F.E. Identification of pathways controlling DNA damage induced mutation in Saccharomyces cerevisiae. DNA Repair 2008, 7, 801-810.
47. Poli, J.; Tsaponina, O.; Crabbe, L.; Keszthelyi, A.; Pantesco, V.; Chabes, A.; Lengronne, A.; Pasero, P. dNTP pools determine fork progression and origin usage under replication stress. EMBO J. 2012, 31, 883-894.
48. Williams, L.N.; Marjavaara, L.; Knowels, G.M.; Schultz, E.M.; Fox, E.J.; Chabes, A.; Herr, A.J. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants. Proc. Natl. Acad. Sci. USA 2015, 112, E2457-E2466.
49. Datta, A.; Schmeits, J.L.; Amin, N.S.; Lau, P.J.; Myung, K.; Kolodner, R.D. Checkpoint-dependent activation of mutagenic repair in Saccharomyces cerevisiae pol3-01 mutants. Mol. Cell 2000, 6, 593-603.
50. Mertz, T.M.; Sharma, S.; Chabes, A.; Shcherbakova, P.V. Colon cancer-associated mutator DNA polymerase delta variant causes expansion of dNTP pools increasing its own infidelity. Proc. Natl. Acad. Sci. USA 2015, 112, E2467-E2476.
51. Stodola, J.L.; Burgers, P.M. Resolving individual steps of Okazaki-fragment maturation at a millisecond timescale. Nat. Struct. Mol. Biol. 2016, 23, 402-408.
52. Kunkel, T.A.; Sabatino, R.D.; Bambara, R.A. Exonucleolytic proofreading by calf thymus DNA polymerase delta. Proc. Natl. Acad. Sci. USA 1987, 84, 4865-4869.
53. Chen, C.W.; Tsao, N.; Huang, L.Y.; Yen, Y.; Liu, X.; Lehman, C.; Wang, Y.H.; Tseng, M.C.; Chen, Y.J.; Ho, Y.C.; et al. The impact of dutpase on ribonucleotide reductase-induced genome instability in cancer cells. Cell Rep. 2016, 16, 1287-1299.
54. Hu, C.M.; Yeh, M.T.; Tsao, N.; Chen, C.W.; Gao, Q.Z.; Chang, C.Y.; Lee, M.H.; Fang, J.M.; Sheu, S.Y.; Lin, C.J.; et al. Tumor cells require thymidylate kinase to prevent dutp incorporation during DNA repair. Cancer Cell 2012, 22, 36-50.
55. Laguette, N.; Sobhian, B.; Casartelli, N.; Ringeard, M.; Chable-Bessia, C.; Segeral, E.; Yatim, A.; Emiliani, S.; Schwartz, O.; Benkirane, M. Samhd1 is the dendritic-and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011, 474, 654-657.
56. Koç, A.; Wheeler, L.J.; Mathews, C.K.; Merrill, G.F. Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools. J. Biol. Chem. 2004, 279, 223-230.
57. Katou, Y.; Kanoh, Y.; Bando, M.; Noguchi, H.; Tanaka, H.; Ashikari, T.; Sugimoto, K.; Shirahige, K. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature 2003, 424, 1078-1083.
58. Sogo, J.M.; Lopes, M.; Foiani, M. Fork reversal and ssNDA accumulation at stalled replication forks owing to checkpoint defects. Science 2002, 297, 599-602.
59. Friedel, A.M.; Pike, B.L.; Gasser, S.M. Atr/Mec1: Coordinating fork stability and repair. Curr. Opin. Cell Biol. 2009, 21, 237-244.
60. Lambert, S.; Froget, B.; Carr, A.M. Arrested replication fork processing: Interplay between checkpoints and recombination. DNA Repair 2007, 6, 1042-1061.
61. Yekezare, M.; Gómez-González, B.; Diffley, J.F.X. Controlling DNA replication origins in response to DNA damage—Inhibit globally, activate locally. J. Cell Sci. 2013, 126, 1297-1306.
62. Tercero, J.A.; Diffley, J.F.X. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Nature 2001, 412, 553-557.
63. Anglana, M.; Apiou, F.; Bensimon, A.; Debatisse, M. Dynamics of DNA replication in mammalian somatic cells: Nucleotide pool modulates origin choice and interorigin spacing. Cell 2003, 114, 385-394.
64. Petermann, E.; Orta, M.L.; Issaeva, N.; Schultz, N.; Helleday, T. Hydroxyurea-stalled replication forks become progressively inactivated and require two different Rad51-mediated pathways for restart and repair. Mol. Cell 2010, 37, 492-502.
65. Sabatinos, S.A.; Mastro, T.L.; Green, M.D.; Forsburg, S.L. A mammalian-like DNA damage response of fission yeast to nucleoside analogs. Genetics 2013, 193, 143-157.
66. Yeeles, J.T.; Poli, J.; Marians, K.J.; Pasero, P. Rescuing stalled or damaged replication forks. Cold Spring Harb. Perspect. Biol. 2013, 5, a012815.
67. Zellweger, R.; Dalcher, D.; Mutreja, K.; Berti, M.; Schmid, J.A.; Herrador, R.; Vindigni, A.; Lopes, M. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. J. Cell Biol. 2015, 208, 563-579.
68. Techer, H.; Koundrioukoff, S.; Carignon, S.; Wilhelm, T.; Millot, G.A.; Lopez, B.S.; Brison, O.; Debatisse, M. Signaling from Mus81-Eme2-dependent DNA damage elicited by Chk1 deficiency modulates replication fork speed and origin usage. Cell Rep. 2016, 14, 1114-1127.
69. Laird, C.; Jaffe, E.; Karpen, G.; Lamb, M.; Nelson, R. Fragile sites in human chromosomes as regions of late-replicating DNA. Trends Genet. 1987, 3, 274-281.
70. Glover, T.W.; Berger, C.; Coyle, J.; Echo, B. DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum. Genet. 1984, 67, 136-142.
71. Paeschke, K.; Bochman, M.L.; Garcia, P.D.; Cejka, P.; Friedman, K.L.; Kowalczykowski, S.C.; Zakian, V.A. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature 2013, 497, 458-462.
72. Samora, C.P.; Saksouk, J.; Goswami, P.; Wade, B.O.; Singleton, M.R.; Bates, P.A.; Lengronne, A.; Costa, A.; Uhlmann, F. Ctf4 links DNA replication with sister chromatid cohesion establishment by recruiting the Chl1 helicase to the replisome. Mol. Cell 2016, 63, 371-384.
73. Cali, F.; Bharti, S.K.; Di Perna, R.; Brosh, R.M., Jr.; Pisani, F.M. Tim/timeless, a member of the replication fork protection complex, operates with the warsaw breakage syndrome DNA helicase Ddx11 in the same fork recovery pathway. Nucleic Acids Res. 2016, 44, 705-717.
74. Gupta, A.; Sharma, S.; Reichenbach, P.; Marjavaara, L.; Nilsson, A.K.; Lingner, J.; Chabes, A.; Rothstein, R.; Chang, M. Telomere length homeostasis responds to changes in intracellular dNTP pools. Genetics 2013, 193, 1095-1105.
75. Chandra, D.; Bratton, S.B.; Person, M.D.; Tian, Y.; Martin, A.G.; Ayres, M.; Fearnhead, H.O.; Gandhi, V.; Tang, D.G. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome c and inhibiting apoptosome. Cell 2006, 125, 1333-1346.
76. Nick McElhinny, S.A.; Watts, B.E.; Kumar, D.; Watt, D.L.; Lundstrom, E.B.; Burgers, P.M.; Johansson, E.; Chabes, A.; Kunkel, T.A. Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases. Proc. Natl. Acad. Sci. USA 2010, 107, 4949-4954.
77. Joyce, C.M. Choosing the right sugar: How polymerases select a nucleotide substrate. Proc. Natl. Acad. Sci. USA 1997, 94, 1619-1622.
78. Reijns, M.A.; Rabe, B.; Rigby, R.E.; Mill, P.; Astell, K.R.; Lettice, L.A.; Boyle, S.; Leitch, A.; Keighren, M.; Kilanowski, F.; et al. Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Cell 2012, 149, 1008-1022.
79. Yao, N.Y.; Schroeder, J.W.; Yurieva, O.; Simmons, L.A.; OʹDonnell, M.E. Cost of rNTP/dNTP pool imbalance at the replication fork. Proc. Natl. Acad. Sci. USA 2013, 110, 12942-12947.
80. Williams, J.S.; Clausen, A.R.; Nick McElhinny, S.A.; Watts, B.E.; Johansson, E.; Kunkel, T.A. Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase varepsilon. DNA Repair 2012, 11, 649-656.
81. Lazzaro, F.; Novarina, D.; Amara, F.; Watt, D.L.; Stone, J.E.; Costanzo, V.; Burgers, P.M.; Kunkel, T.A.; Plevani, P.; Muzi-Falconi, M. Rnase H and postreplication repair protect cells from ribonucleotides incorporated in DNA. Mol. Cell 2012, 45, 99-110.
82. Nick McElhinny, S.A.; Kumar, D.; Clark, A.B.; Watt, D.L.; Watts, B.E.; Lundström, E.-B.; Johansson, E.; Chabes, A.; Kunkel, T.A. Genome instability due to ribonucleotide incorporation into DNA. Nat. Chem. Biol. 2010, 6, 774-781.
83. Kim, N.; Huang, S.N.; Williams, J.S.; Li, Y.C.; Clark, A.B.; Cho, J.E.; Kunkel, T.A.; Pommier, Y.; Jinks-Robertson, S. Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 2011, 332, 1561-1564.
84. Sparks, J.L.; Burgers, P.M. Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic ribonucleotides. EMBO J. 2015, 34, 1259-1269.
85. Clausen, A.R.; Zhang, S.; Burgers, P.M.; Lee, M.Y.; Kunkel, T.A. Ribonucleotide incorporation, proofreading and bypass by human DNA polymerase delta. DNA Repair 2013, 12, 121-127.
86. Williams, J.S.; Lujan, S.A.; Kunkel, T.A. Processing ribonucleotides incorporated during eukaryotic DNA replication. Nat. Rev. Mol. Cell Biol. 2016, 17, 350-363.
87. Probst, A.V.; Dunleavy, E.; Almouzni, G. Epigenetic inheritance during the cell cycle. Nat. Rev. Mol. Cell Biol. 2009, 10, 192-206.
88. Natsume, R.; Eitoku, M.; Akai, Y.; Sano, N.; Horikoshi, M.; Senda, T. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature 2007, 446, 338-341.
89. Tagami, H.; Ray-Gallet, D.; Almouzni, G.; Nakatani, Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 2004, 116, 51-61.
90. Groth, A.; Rocha, W.; Verreault, A.; Almouzni, G. Chromatin challenges during DNA replication and repair. Cell 2007, 128, 721-733.
91. Jasencakova, Z.; Groth, A. Replication stress, a source of epigenetic aberrations in cancer? Bioessays 2010, 32, 847-855.
92. Papadopoulou, C.; Guilbaud, G.; Schiavone, D.; Sale, J.E. Nucleotide pool depletion induces g-quadruplex-dependent perturbation of gene expression. Cell Rep. 2015, 13, 2491-2503.
93. Shanbhag, N.M.; Rafalska-Metcalf, I.U.; Balane-Bolivar, C.; Janicki, S.M.; Greenberg, R.A. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 2010, 141, 970-981.
94. Ayrapetov, M.K.; Gursoy-Yuzugullu, O.; Xu, C.; Xu, Y.; Price, B.D. DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin. Proc. Natl. Acad. Sci. USA 2014, 111, 9169-9174.
95. Aye, Y.; Li, M.; Long, M.J.; Weiss, R.S. Ribonucleotide reductase and cancer: Biological mechanisms and targeted therapies. Oncogene 2015, 34, 2011-2021.
96. Hanft, V.N.; Fruchtman, S.R.; Pickens, C.V.; Rosse, W.F.; Howard, T.A.; Ware, R.E. Acquired DNA mutations associated with in vivo hydroxyurea exposure. Blood 2000, 95, 3589-3593.
97. Steinberg, M.H.; Nagel, R.L.; Brugnara, C. Cellular effects of hydroxyurea in Hb SC disease. Br. J. Haematol. 1997, 98, 838-844.
98. Arlt, M.F.; Ozdemir, A.C.; Birkeland, S.R.; Wilson, T.E.; Glover, T.W. Hydroxyurea induces de novo copy number variants in human cells. Proc. Natl. Acad. Sci. USA 2011, 108, 17360-17365.
99. Kunz, B.A.; Kohalmi, S.E.; Kunkel, T.A.; Mathews, C.K.; McIntosh, E.M.; Reidy, J.A. Deoxyribonucleoside triphosphate levels: A critical factor in the maintenance of genetic stability. Mutat. Res. Rev. Genet. Toxicol. 1994, 318, 1-64.
100. Kumar, D.; Abdulovic, A.L.; Viberg, J.; Nilsson, A.K.; Kunkel, T.A.; Chabes, A. Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools. Nucleic Acids Res. 2011, 39, 1360-1371.
101. Kumar, D.; Viberg, J.; Nilsson, A.K.; Chabes, A. Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint. Nucleic Acids Res. 2010, 38, 3975-3983.
102. Ahluwalia, D.; Schaaper, R.M. Hypermutability and error catastrophe due to defects in ribonucleotide reductase. Proc. Natl. Acad. Sci. USA 2013, 110, 18596-18601.
103. Watt, D.L.; Buckland, R.J.; Lujan, S.A.; Kunkel, T.A.; Chabes, A. Genome-wide analysis of the specificity and mechanisms of replication infidelity driven by imbalanced dNTP pools. Nucleic Acids Res. 2016, 44, 1669-1680.
104. Gemble, S.; Buhagiar-Labarchede, G.; Onclercq-Delic, R.; Biard, D.; Lambert, S.; Amor-Gueret, M. A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation. J. Cell Sci. 2016, 129, 3167-3177.
105. Gemble, S.; Ahuja, A.; Buhagiar-Labarchede, G.; Onclercq-Delic, R.; Dairou, J.; Biard, D.S.; Lambert, S.; Lopes, M.; Amor-Gueret, M. Pyrimidine pool disequilibrium induced by a cytidine deaminase deficiency inhibits PARP-1 activity, leading to the under replication of DNA. PLoS Genet. 2015, 11, e1005384.
106. Hastak, K.; Paul, R.K.; Agarwal, M.K.; Thakur, V.S.; Amin, A.R.; Agrawal, S.; Sramkoski, R.M.; Jacobberger, J.W.; Jackson, M.W.; Stark, G.R.; et al. DNA synthesis from unbalanced nucleotide pools causes limited DNA damage that triggers Atr-Chk1-dependent p53 activation. Proc. Natl. Acad. Sci. USA 2008, 105, 6314-6319.
107. Ke, P.Y.; Kuo, Y.Y.; Hu, C.M.; Chang, Z.F. Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability. Genes Dev. 2005, 19, 1920-1933.
108. Tanaka, H.; Arakawa, H.; Yamaguchi, T.; Shiraishi, K.; Fukuda, S.; Matsui, K.; Takei, Y.; Nakamura, Y. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 2000, 404, 42-49.
109. Shaibani, A.; Shchelochkov, O.A.; Zhang, S.; Katsonis, P.; Lichtarge, O.; Wong, L.J.; Shinawi, M. Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch. Neurol. 2009, 66, 1028-1032.
110. Tyynismaa, H.; Ylikallio, E.; Patel, M.; Molnar, M.J.; Haller, R.G.; Suomalainen, A. A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtdna deletions. Am. J. Hum. Genet. 2009, 85, 290-295.
111. Mandel, H.; Szargel, R.; Labay, V.; Elpeleg, O.; Saada, A.; Shalata, A.; Anbinder, Y.; Berkowitz, D.; Hartman, C.; Barak, M., et al. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat. Genet. 2001, 29, 337-341.
112. Saada, A.; Shaag, A.; Mandel, H.; Nevo, Y.; Eriksson, S.; Elpeleg, O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat. Genet. 2001, 29, 342-344.
113. Wang, L. Mitochondrial purine and pyrimidine metabolism and beyond. Nucleosides Nucleotides Nucleic Acids 2016, 35, 578-594.
114. Gonzalez-Vioque, E.; Torres-Torronteras, J.; Andreu, A.L.; Marti, R. Limited dCTP availability accounts for mitochondrial DNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). PLoS Genet. 2011, 7, e1002035.
115. Nikkanen, J.; Forsstrom, S.; Euro, L.; Paetau, I.; Kohnz, R.A.; Wang, L.; Chilov, D.; Viinamaki, J.; Roivainen, A.; Marjamaki, P.; et al. Mitochondrial DNA replication defects disturb cellular dNTP pools and remodel one-carbon metabolism. Cell Metab. 2016, 23, 635-648.
116. Chabosseau, P.; Buhagiar-Labarchede, G.; Onclercq-Delic, R.; Lambert, S.; Debatisse, M.; Brison, O.; Amor-Gueret, M. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in bloom syndrome. Nat. Commun. 2011, doi:10.1038/ncomms1363.
117. Saldivar, J.C.; Miuma, S.; Bene, J.; Hosseini, S.A.; Shibata, H.; Sun, J.; Wheeler, L.J.; Mathews, C.K.; Huebner, K. Initiation of genome instability and preneoplastic processes through loss of FHIT expression. PLoS Genet. 2012, 8, e1003077.
118. Xu, X.; Page, J.L.; Surtees, J.A.; Liu, H.; Lagedrost, S.; Lu, Y.; Bronson, R.; Alani, E.; Nikitin, A.Y.; Weiss, R.S. Broad overexpression of ribonucleotide reductase genes in mice specifically induces lung neoplasms. Cancer Res. 2008, 68, 2652-2660.
119. D’Angiolella, V.; Donato, V.; Forrester, F.M.; Jeong, Y.T.; Pellacani, C.; Kudo, Y.; Saraf, A.; Florens, L.; Washburn, M.P.; Pagano, M. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell 2012, 149, 1023-1034.
120. Kohnken, R.; Kodigepalli, K.M.; Wu, L. Regulation of deoxynucleotide metabolism in cancer: Novel mechanisms and therapeutic implications. Mol. Cancer 2015, doi:10.1186/s12943-015-0446-6.
121. Fishel, R.; Lescoe, M.K.; Rao, M.R.; Copeland, N.G.; Jenkins, N.A.; Garber, J.; Kane, M.; Kolodner, R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1993, 75, 1027-1038.
122. Leach, F.S.; Nicolaides, N.C.; Papadopoulos, N.; Liu, B.; Jen, J.; Parsons, R.; Peltomaki, P.; Sistonen, P.; Aaltonen, L.A.; Nystrom-Lahti, M.; et al. Mutations of a muts homolog in hereditary nonpolyposis colorectal cancer. Cell 1993, 75, 1215-1225.
123. Palles, C.; Cazier, J.B.; Howarth, K.M.; Domingo, E.; Jones, A.M.; Broderick, P.; Kemp, Z.; Spain, S.L.; Guarino, E.; Salguero, I.; et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 2013, 45, 136-144.
124. Rentoft, M.; Lindell, K.; Tran, P.; Chabes, A.L.; Buckland, R.J.; Watt, D.L.; Marjavaara, L.; Nilsson, A.K.; Melin, B.; Trygg, J.; et al. Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance. Proc. Natl. Acad. Sci. USA 2016, 113, 4723-4728.
125. Rice, G.I.; Bond, J.; Asipu, A.; Brunette, R.L.; Manfield, I.W.; Carr, I.M.; Fuller, J.C.; Jackson, R.M.; Lamb, T.; Briggs, T.A.; et al. Mutations involved in aicardi-goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat. Genet. 2009, 41, 829-832.
126. Beloglazova, N.; Flick, R.; Tchigvintsev, A.; Brown, G.; Popovic, A.; Nocek, B.; Yakunin, A.F. Nuclease activity of the human SAMHD1 protein implicated in the aicardi-goutieres syndrome and HIV-1 restriction. J. Biol. Chem. 2013, 288, 8101-8110.
127. Nonaka, M.; Tsuchimoto, D.; Sakumi, K.; Nakabeppu, Y. Mouse RS21-C6 is a mammalian 2’-deoxycytidine 5’-triphosphate pyrophosphohydrolase that prefers 5-iodocytosine. FEBS J. 2009, 276, 1654-1666.
128. Requena, C.E.; Perez-Moreno, G.; Ruiz-Perez, L.M.; Vidal, A.E.; Gonzalez-Pacanowska, D. The NTP pyrophosphatase DCTPP1 contributes to the homoeostasis and cleansing of the dNTP pool in human cells. Biochem. J. 2014, 459, 171-180.
129. Halazonetis, T.D.; Gorgoulis, V.G.; Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 2008, 319, 1352-1355.
130. Bester, A.C.; Roniger, M.; Oren, Y.S.; Im, M.M.; Sarni, D.; Chaoat, M.; Bensimon, A.; Zamir, G.; Shewach, D.S.; Kerem, B. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011, 145, 435-446.
131. McKinnon, P.J. DNA repair deficiency and neurological disease. Nat. Rev. Neurosci. 2009, 10, 100-112.
132. McKinnon, P.J. Maintaining genome stability in the nervous system. Nat. Neurosci. 2013, 16, 1523-1529.
133. Schoors, S.; Bruning, U.; Missiaen, R.; Queiroz, K.C.; Borgers, G.; Elia, I.; Zecchin, A.; Cantelmo, A.R.; Christen, S.; Goveia, J.; et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 2015, 520, 192-197.
134. Kuzminov, A. Inhibition of DNA synthesis facilitates expansion of low-complexity repeats: Is strand slippage stimulated by transient local depletion of specific dNTPs? Bioessays 2013, 35, 306-313.
135. Leffak, M. Hypothesis: Local dNTP depletion as the cause of microsatellite repeat instability during replication (comment on doi 10.1002/bies.201200128). Bioessays 2013, doi:10.1002/bies.201300026.
136. Pontarin, G.; Fijolek, A.; Pizzo, P.; Ferraro, P.; Rampazzo, C.; Pozzan, T.; Thelander, L.; Reichard, P.A.; Bianchi, V. Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage. Proc. Natl. Acad. Sci. USA 2008, 105, 17801-17806.
137. Zhang, Y.W.; Jones, T.L.; Martin, S.E.; Caplen, N.J.; Pommier, Y. Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. J. Biol. Chem. 2009, 284, 18085-18095.
138. Niida, H.; Katsuno, Y.; Sengoku, M.; Shimada, M.; Yukawa, M.; Ikura, M.; Ikura, T.; Kohno, K.; Shima, H.; Suzuki, H.; et al. Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. Genes Dev. 2010, 24, 333-338.