DNA Damage Bypass (Homo sapiens)

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1-3nucleoplasmdNTPPol eta:lesioned DNA template inserted with correct base complementElongated DNA template with bypassed lesionPol eta proteinHREV1:lesioned DNA template with misinserted basesHREV7Pol zeta complexHREV3HREV1:damaged DNA template complexdamaged DNA substrateHREV1Pol eta:damaged DNA template complexPol zeta:damaged DNA template complex


Description

In addition to various processes for removing damaging lesions from the DNA, cells have developed specific mechanisms for tolerating unexcised damages during the replication of the genome. Such processes are collectively called DNA damage bypass pathways. Several proteins including novel Y-family polymerases that have been recently identified in multitude of organisms are involved in this process.
Translesion synthesis (TLS) or replicative bypass of damaged bases that are known to arrest high fidelity, highly processive polymerases involved in DNA replication is carried out by error-prone polymerases Pol zeta, Pol eta and Rev3 protein among others. TLS is implicated in UV and chemical induced mutagenesis of normal human cells where lesions in the replicating genome are carried over to the newly formed daughter cells.
All these 3 enzymes are found to lack 3’->5’ exonuclease activity, while exhibiting low fidelity, weak processivity and sufficient polymerase activities. An outline of the bypass synthesis by these 3 enzymes is annotated here. Complete details of damage recognition and discrimination, initiation of specific polymerase activity and the finer mechanisms are yet to be elucidated.

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Bibliography

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  1. Friedberg EC, Lehmann AR, Fuchs RP.; ''Trading places: how do DNA polymerases switch during translesion DNA synthesis?''; PubMed Europe PMC Scholia
  2. Cohn MA, Kowal P, Yang K, Haas W, Huang TT, Gygi SP, D'Andrea AD.; ''A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway.''; PubMed Europe PMC Scholia
  3. Notenboom V, Hibbert RG, van Rossum-Fikkert SE, Olsen JV, Mann M, Sixma TK.; ''Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification.''; PubMed Europe PMC Scholia
  4. Davis EJ, Lachaud C, Appleton P, Macartney TJ, Näthke I, Rouse J.; ''DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage.''; PubMed Europe PMC Scholia
  5. Kosarek JN, Woodruff RV, Rivera-Begeman A, Guo C, D'Souza S, Koonin EV, Walker GC, Friedberg EC.; ''Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts.''; PubMed Europe PMC Scholia
  6. Saugar I, Ortiz-Bazán MÁ, Tercero JA.; ''Tolerating DNA damage during eukaryotic chromosome replication.''; PubMed Europe PMC Scholia
  7. Nelson JR, Lawrence CW, Hinkle DC.; ''Deoxycytidyl transferase activity of yeast REV1 protein.''; PubMed Europe PMC Scholia
  8. Carlson KD, Johnson RE, Prakash L, Prakash S, Washington MT.; ''Human DNA polymerase kappa forms nonproductive complexes with matched primer termini but not with mismatched primer termini.''; PubMed Europe PMC Scholia
  9. Ulrich HD.; ''Timing and spacing of ubiquitin-dependent DNA damage bypass.''; PubMed Europe PMC Scholia
  10. Chang CN, Feng MJ, Chen YL, Yuan RH, Jeng YM.; ''p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression.''; PubMed Europe PMC Scholia
  11. Vasquez-Del Carpio R, Silverstein TD, Lone S, Swan MK, Choudhury JR, Johnson RE, Prakash S, Prakash L, Aggarwal AK.; ''Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion.''; PubMed Europe PMC Scholia
  12. Centore RC, Yazinski SA, Tse A, Zou L.; ''Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response.''; PubMed Europe PMC Scholia
  13. Zhu F, Zhang M.; ''DNA polymerase zeta: new insight into eukaryotic mutagenesis and mammalian embryonic development.''; PubMed Europe PMC Scholia
  14. Matsuda T, Bebenek K, Masutani C, Hanaoka F, Kunkel TA.; ''Low fidelity DNA synthesis by human DNA polymerase-eta.''; PubMed Europe PMC Scholia
  15. Terai K, Abbas T, Jazaeri AA, Dutta A.; ''CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.''; PubMed Europe PMC Scholia
  16. Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M, Ohmori H, Vaziri C.; ''Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest.''; PubMed Europe PMC Scholia
  17. Emanuele MJ, Ciccia A, Elia AE, Elledge SJ.; ''Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate.''; PubMed Europe PMC Scholia
  18. Yoon JH, Bhatia G, Prakash S, Prakash L.; ''Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases kappa and zeta in human cells.''; PubMed Europe PMC Scholia
  19. Zhang Y, Wu X, Rechkoblit O, Geacintov NE, Taylor JS, Wang Z.; ''Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion.''; PubMed Europe PMC Scholia
  20. Bienko M, Green CM, Sabbioneda S, Crosetto N, Matic I, Hibbert RG, Begovic T, Niimi A, Mann M, Lehmann AR, Dikic I.; ''Regulation of translesion synthesis DNA polymerase eta by monoubiquitination.''; PubMed Europe PMC Scholia
  21. Lehmann AR.; ''Replication of UV-damaged DNA: new insights into links between DNA polymerases, mutagenesis and human disease.''; PubMed Europe PMC Scholia
  22. Hara K, Hashimoto H, Murakumo Y, Kobayashi S, Kogame T, Unzai S, Akashi S, Takeda S, Shimizu T, Sato M.; ''Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1.''; PubMed Europe PMC Scholia
  23. Shiyanov P, Nag A, Raychaudhuri P.; ''Cullin 4A associates with the UV-damaged DNA-binding protein DDB.''; PubMed Europe PMC Scholia
  24. Nelson JR, Lawrence CW, Hinkle DC.; ''Thymine-thymine dimer bypass by yeast DNA polymerase zeta.''; PubMed Europe PMC Scholia
  25. Lee YS, Gregory MT, Yang W.; ''Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.''; PubMed Europe PMC Scholia
  26. Fischhaber PL, Gerlach VL, Feaver WJ, Hatahet Z, Wallace SS, Friedberg EC.; ''Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides.''; PubMed Europe PMC Scholia
  27. Washington MT, Minko IG, Johnson RE, Wolfle WT, Harris TM, Lloyd RS, Prakash S, Prakash L.; ''Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa.''; PubMed Europe PMC Scholia
  28. Lior-Hoffmann L, Wang L, Wang S, Geacintov NE, Broyde S, Zhang Y.; ''Preferred WMSA catalytic mechanism of the nucleotidyl transfer reaction in human DNA polymerase κ elucidates error-free bypass of a bulky DNA lesion.''; PubMed Europe PMC Scholia
  29. Kannouche PL, Wing J, Lehmann AR.; ''Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage.''; PubMed Europe PMC Scholia
  30. Ohashi E, Bebenek K, Matsuda T, Feaver WJ, Gerlach VL, Friedberg EC, Ohmori H, Kunkel TA.; ''Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene.''; PubMed Europe PMC Scholia
  31. Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.; ''Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.''; PubMed Europe PMC Scholia
  32. Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK.; ''Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing.''; PubMed Europe PMC Scholia
  33. Johnson RE, Washington MT, Haracska L, Prakash S, Prakash L.; ''Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions.''; PubMed Europe PMC Scholia
  34. Lin W, Xin H, Zhang Y, Wu X, Yuan F, Wang Z.; ''The human REV1 gene codes for a DNA template-dependent dCMP transferase.''; PubMed Europe PMC Scholia
  35. Ohashi E, Murakumo Y, Kanjo N, Akagi J, Masutani C, Hanaoka F, Ohmori H.; ''Interaction of hREV1 with three human Y-family DNA polymerases.''; PubMed Europe PMC Scholia
  36. Christov PP, Yamanaka K, Choi JY, Takata K, Wood RD, Guengerich FP, Lloyd RS, Rizzo CJ.; ''Replication of the 2,6-diamino-4-hydroxy-N(5)-(methyl)-formamidopyrimidine (MeFapy-dGuo) adduct by eukaryotic DNA polymerases.''; PubMed Europe PMC Scholia
  37. Neal JA, Fletcher KL, McCormick JJ, Maher VM.; ''The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE).''; PubMed Europe PMC Scholia
  38. Masutani C, Kusumoto R, Iwai S, Hanaoka F.; ''Mechanisms of accurate translesion synthesis by human DNA polymerase eta.''; PubMed Europe PMC Scholia
  39. Gibbs PE, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW, Maher VM.; ''The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light.''; PubMed Europe PMC Scholia
  40. Jung YS, Liu G, Chen X.; ''Pirh2 E3 ubiquitin ligase targets DNA polymerase eta for 20S proteasomal degradation.''; PubMed Europe PMC Scholia
  41. Zhang Y, Yuan F, Wu X, Wang M, Rechkoblit O, Taylor JS, Geacintov NE, Wang Z.; ''Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro.''; PubMed Europe PMC Scholia
  42. Ghosal G, Leung JW, Nair BC, Fong KW, Chen J.; ''Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis.''; PubMed Europe PMC Scholia
  43. Murakumo Y, Roth T, Ishii H, Rasio D, Numata S, Croce CM, Fishel R.; ''A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2.''; PubMed Europe PMC Scholia
  44. Xie W, Yang X, Xu M, Jiang T.; ''Structural insights into the assembly of human translesion polymerase complexes.''; PubMed Europe PMC Scholia
  45. Yang IY, Miller H, Wang Z, Frank EG, Ohmori H, Hanaoka F, Moriya M.; ''Mammalian translesion DNA synthesis across an acrolein-derived deoxyguanosine adduct. Participation of DNA polymerase eta in error-prone synthesis in human cells.''; PubMed Europe PMC Scholia
  46. Sokhansanj BA, Rodrigue GR, Fitch JP, Wilson DM.; ''A quantitative model of human DNA base excision repair. I. Mechanistic insights.''; PubMed Europe PMC Scholia
  47. Bomar MG, D'Souza S, Bienko M, Dikic I, Walker GC, Zhou P.; ''Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.''; PubMed Europe PMC Scholia
  48. Lindahl T, Wood RD.; ''Quality control by DNA repair.''; PubMed Europe PMC Scholia
  49. Guo C, Fischhaber PL, Luk-Paszyc MJ, Masuda Y, Zhou J, Kamiya K, Kisker C, Friedberg EC.; ''Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis.''; PubMed Europe PMC Scholia
  50. Haracska L, Unk I, Johnson RE, Phillips BB, Hurwitz J, Prakash L, Prakash S.; ''Stimulation of DNA synthesis activity of human DNA polymerase kappa by PCNA.''; PubMed Europe PMC Scholia
  51. Jung YS, Hakem A, Hakem R, Chen X.; ''Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis.''; PubMed Europe PMC Scholia
  52. Mosbech A, Gibbs-Seymour I, Kagias K, Thorslund T, Beli P, Povlsen L, Nielsen SV, Smedegaard S, Sedgwick G, Lukas C, Hartmann-Petersen R, Lukas J, Choudhary C, Pocock R, Bekker-Jensen S, Mailand N.; ''DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks.''; PubMed Europe PMC Scholia
  53. Friedberg EC, Fischhaber PL, Kisker C.; ''Error-prone DNA polymerases: novel structures and the benefits of infidelity.''; PubMed Europe PMC Scholia
  54. Giannakopoulos NV, Luo JK, Papov V, Zou W, Lenschow DJ, Jacobs BS, Borden EC, Li J, Virgin HW, Zhang DE.; ''Proteomic identification of proteins conjugated to ISG15 in mouse and human cells.''; PubMed Europe PMC Scholia
  55. Everson RB, Randerath E, Santella RM, Cefalo RC, Avitts TA, Randerath K.; ''Detection of smoking-related covalent DNA adducts in human placenta.''; PubMed Europe PMC Scholia
  56. Murakumo Y, Ogura Y, Ishii H, Numata S, Ichihara M, Croce CM, Fishel R, Takahashi M.; ''Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7.''; PubMed Europe PMC Scholia
  57. Haracska L, Acharya N, Unk I, Johnson RE, Hurwitz J, Prakash L, Prakash S.; ''A single domain in human DNA polymerase iota mediates interaction with PCNA: implications for translesion DNA synthesis.''; PubMed Europe PMC Scholia
  58. Wojtaszek J, Lee CJ, D'Souza S, Minesinger B, Kim H, D'Andrea AD, Walker GC, Zhou P.; ''Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) ζ, and Pol κ.''; PubMed Europe PMC Scholia
  59. Yoon JH, Roy Choudhury J, Park J, Prakash S, Prakash L.; ''A role for DNA polymerase θ in promoting replication through oxidative DNA lesion, thymine glycol, in human cells.''; PubMed Europe PMC Scholia
  60. Takata K, Wood RD.; ''Bypass specialists operate together.''; PubMed Europe PMC Scholia
  61. Huang TT, Nijman SM, Mirchandani KD, Galardy PJ, Cohn MA, Haas W, Gygi SP, Ploegh HL, Bernards R, D'Andrea AD.; ''Regulation of monoubiquitinated PCNA by DUB autocleavage.''; PubMed Europe PMC Scholia
  62. Avkin S, Goldsmith M, Velasco-Miguel S, Geacintov N, Friedberg EC, Livneh Z.; ''Quantitative analysis of translesion DNA synthesis across a benzo[a]pyrene-guanine adduct in mammalian cells: the role of DNA polymerase kappa.''; PubMed Europe PMC Scholia
  63. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S.; ''RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO.''; PubMed Europe PMC Scholia
  64. Ohashi E, Ogi T, Kusumoto R, Iwai S, Masutani C, Hanaoka F, Ohmori H.; ''Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa.''; PubMed Europe PMC Scholia
  65. Pence MG, Blans P, Zink CN, Fishbein JC, Perrino FW.; ''Bypass of N²-ethylguanine by human DNA polymerase κ.''; PubMed Europe PMC Scholia
  66. Ohashi E, Hanafusa T, Kamei K, Song I, Tomida J, Hashimoto H, Vaziri C, Ohmori H.; ''Identification of a novel REV1-interacting motif necessary for DNA polymerase kappa function.''; PubMed Europe PMC Scholia
  67. Davies AA, Huttner D, Daigaku Y, Chen S, Ulrich HD.; ''Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a.''; PubMed Europe PMC Scholia
  68. Garg P, Burgers PM.; ''Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1.''; PubMed Europe PMC Scholia
  69. Wood A, Garg P, Burgers PM.; ''A ubiquitin-binding motif in the translesion DNA polymerase Rev1 mediates its essential functional interaction with ubiquitinated proliferating cell nuclear antigen in response to DNA damage.''; PubMed Europe PMC Scholia
  70. Shachar S, Ziv O, Avkin S, Adar S, Wittschieben J, Reissner T, Chaney S, Friedberg EC, Wang Z, Carell T, Geacintov N, Livneh Z.; ''Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals.''; PubMed Europe PMC Scholia
  71. Haracska L, Prakash L, Prakash S.; ''Role of human DNA polymerase kappa as an extender in translesion synthesis.''; PubMed Europe PMC Scholia
  72. Bienko M, Green CM, Crosetto N, Rudolf F, Zapart G, Coull B, Kannouche P, Wider G, Peter M, Lehmann AR, Hofmann K, Dikic I.; ''Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis.''; PubMed Europe PMC Scholia
  73. Park JM, Yang SW, Yu KR, Ka SH, Lee SW, Seol JH, Jeon YJ, Chung CH.; ''Modification of PCNA by ISG15 plays a crucial role in termination of error-prone translesion DNA synthesis.''; PubMed Europe PMC Scholia
  74. Wojtaszek J, Liu J, D'Souza S, Wang S, Xue Y, Walker GC, Zhou P.; ''Multifaceted recognition of vertebrate Rev1 by translesion polymerases ζ and κ.''; PubMed Europe PMC Scholia
  75. Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK.; ''Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota.''; PubMed Europe PMC Scholia
  76. Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H.; ''Structural basis of recruitment of DNA polymerase ζ by interaction between REV1 and REV7 proteins.''; PubMed Europe PMC Scholia
  77. Wolfle WT, Washington MT, Prakash L, Prakash S.; ''Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions.''; PubMed Europe PMC Scholia

History

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115091view17:04, 25 January 2021ReactomeTeamReactome version 75
113533view12:01, 2 November 2020ReactomeTeamReactome version 74
112731view16:13, 9 October 2020ReactomeTeamReactome version 73
101647view11:51, 1 November 2018ReactomeTeamreactome version 66
101183view21:39, 31 October 2018ReactomeTeamreactome version 65
100709view20:11, 31 October 2018ReactomeTeamreactome version 64
100259view16:56, 31 October 2018ReactomeTeamreactome version 63
99812view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99356view12:48, 31 October 2018ReactomeTeamreactome version 62
93950view13:47, 16 August 2017ReactomeTeamreactome version 61
93543view11:26, 9 August 2017ReactomeTeamreactome version 61
86644view09:23, 11 July 2016ReactomeTeamreactome version 56
83335view10:49, 18 November 2015ReactomeTeamVersion54
81489view13:01, 21 August 2015ReactomeTeamVersion53
76966view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76671view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
76000view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75703view11:04, 10 June 2014ReactomeTeamReactome 48 Update
75059view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74703view08:46, 30 April 2014ReactomeTeamReactome46
45195view10:04, 7 October 2011MartijnVanIerselOntology Term : 'DNA repair pathway' added !
42026view21:51, 4 March 2011MaintBotAutomatic update
39829view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Elongated DNA

template with bypassed lesion

UnknownREACT_3182 (Reactome)
HREV1 ProteinREACT_14374 (Reactome)
HREV1:damaged

DNA template complex

ComplexREACT_3664 (Reactome)
HREV1:lesioned

DNA template with misinserted bases

ComplexREACT_5530 (Reactome)
HREV3 ProteinQ9UID5 (UniProt)
HREV7 ProteinQ9UI95 (UniProt)
Pol eta protein ProteinQ9Y253 (UniProt)
Pol eta:damaged DNA

template complex

ComplexREACT_2831 (Reactome)
Pol eta:lesioned DNA

template inserted with correct base complement

ComplexREACT_3971 (Reactome)
Pol zeta complex ComplexREACT_5310 (Reactome)
Pol zeta:damaged

DNA template complex

ComplexREACT_5394 (Reactome)
dNTP UnknownREACT_2960 (Reactome)
damaged DNA

substrate

UnknownREACT_2765 (Reactome)

Annotated Interactions

No annotated interactions

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