skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo

Abstract

Cells are constantly exposed to endogenous and exogenous chemical and physical agents that damage their genome by forming DNA lesions. These lesions interfere with the normal functions of DNA such as transcription and replication, and need to be either repaired or tolerated. DNA lesions are accurately removed via various repair pathways. In contrast, tolerance mechanisms do not remove lesions but only allow replication to proceed despite the presence of unrepaired lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS), which is an error-prone strategy and an accurate strategy based on homologous recombination (homology-dependent gap repair [HDGR]). Thus, the mutation frequency reflects the relative extent to which the two tolerance pathways operate in vivo. In the present paper, we review the present understanding of the mechanisms of TLS and HDGR and propose a novel and comprehensive view of the way both strategies interact and are regulated in vivo.

Authors:
 [1];  [1];  [1]
  1. DNA Damage Tolerance CNRS, Marseille (France); Institut Paoli-Calmettes, Marseille (France); Aix-Marseille Univ., Marseille (France); Inserm, Marseille (France)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1559160
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Toxicological research
Additional Journal Information:
Journal Volume: 34; Journal Issue: 4; Journal ID: ISSN 1976-8257
Publisher:
Korean Society of Toxicology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Fujii, Shingo, Isogawa, Asako, and Fuchs, Robert P. Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo. United States: N. p., 2018. Web. doi:10.5487/TR.2018.34.4.297.
Fujii, Shingo, Isogawa, Asako, & Fuchs, Robert P. Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo. United States. doi:10.5487/TR.2018.34.4.297.
Fujii, Shingo, Isogawa, Asako, and Fuchs, Robert P. Mon . "Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo". United States. doi:10.5487/TR.2018.34.4.297. https://www.osti.gov/servlets/purl/1559160.
@article{osti_1559160,
title = {Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo},
author = {Fujii, Shingo and Isogawa, Asako and Fuchs, Robert P.},
abstractNote = {Cells are constantly exposed to endogenous and exogenous chemical and physical agents that damage their genome by forming DNA lesions. These lesions interfere with the normal functions of DNA such as transcription and replication, and need to be either repaired or tolerated. DNA lesions are accurately removed via various repair pathways. In contrast, tolerance mechanisms do not remove lesions but only allow replication to proceed despite the presence of unrepaired lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS), which is an error-prone strategy and an accurate strategy based on homologous recombination (homology-dependent gap repair [HDGR]). Thus, the mutation frequency reflects the relative extent to which the two tolerance pathways operate in vivo. In the present paper, we review the present understanding of the mechanisms of TLS and HDGR and propose a novel and comprehensive view of the way both strategies interact and are regulated in vivo.},
doi = {10.5487/TR.2018.34.4.297},
journal = {Toxicological research},
number = 4,
volume = 34,
place = {United States},
year = {2018},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:

Works referenced in this record:

RecA-Dependent Recovery of Arrested DNA Replication Forks
journal, December 2003


Discontinuities in the DNA synthesized in an Excision-defective strain of Escherichia coli following ultraviolet irradiation
journal, January 1968


Replication fork stalling and cell cycle arrest in UV-irradiated Escherichia coli
journal, March 2007

  • Rudolph, C. J.; Upton, A. L.; Lloyd, R. G.
  • Genes & Development, Vol. 21, Issue 6
  • DOI: 10.1101/gad.417607

Dynamics of Leading-Strand Lesion Skipping by the Replisome
journal, December 2013


Exchanges between DNA strands in ultraviolet-irradiated Escherichia coli
journal, October 1971


Gaps and forks in DNA replication: Rediscovering old models
journal, December 2006


Multiple Mechanisms Control Chromosome Integrity after Replication Fork Uncoupling and Restart at Irreparable UV Lesions
journal, January 2006


Ubiquitin-dependent DNA damage bypass is separable from genome replication
journal, May 2010

  • Daigaku, Yasukazu; Davies, Adelina A.; Ulrich, Helle D.
  • Nature, Vol. 465, Issue 7300
  • DOI: 10.1038/nature09097

Nascent DNA processing by RecJ favors lesion repair over translesion synthesis at arrested replication forks in Escherichia coli
journal, June 2006

  • Courcelle, C. T.; Chow, K. -H.; Casey, A.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 24
  • DOI: 10.1073/pnas.0600785103

Mutagenesis of the replication point by nitrosoguanidine: Map and pattern of replication of the Escherichia coli chromosome
journal, May 1968


A model for replication repair in mammalian cells
journal, March 1976


Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation.
journal, January 1975

  • Lehman, A. R.; Kirk-Bell, S.; Arlett, C. F.
  • Proceedings of the National Academy of Sciences, Vol. 72, Issue 1
  • DOI: 10.1073/pnas.72.1.219

DNA damage tolerance by recombination: Molecular pathways and DNA structures
journal, August 2016


Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells
journal, March 2013

  • Izhar, L.; Ziv, O.; Cohen, I. S.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 16
  • DOI: 10.1073/pnas.1216894110

Rad8Rad5/Mms2–Ubc13 ubiquitin ligase complex controls translesion synthesis in fission yeast
journal, May 2010

  • Coulon, Stéphane; Ramasubramanyan, Sharada; Alies, Carole
  • The EMBO Journal, Vol. 29, Issue 12
  • DOI: 10.1038/emboj.2010.87

Error-Prone Repair DNA Polymerases in Prokaryotes and Eukaryotes
journal, June 2002


The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
journal, June 1999

  • Masutani, Chikahide; Kusumoto, Rika; Yamada, Ayumi
  • Nature, Vol. 399, Issue 6737
  • DOI: 10.1038/21447

hRAD30 Mutations in the Variant Form of Xeroderma Pigmentosum
journal, July 1999


UmuD'2C is an error-prone DNA polymerase, Escherichia coli pol V
journal, August 1999

  • Tang, M.; Shen, X.; Frank, E. G.
  • Proceedings of the National Academy of Sciences, Vol. 96, Issue 16
  • DOI: 10.1073/pnas.96.16.8919

Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light
journal, January 1977

  • Kato, Takesi; Shinoura, Yukiko
  • MGG Molecular & General Genetics, Vol. 156, Issue 2
  • DOI: 10.1007/BF00283484

Influence of RecA protein on induced mutagenesis
journal, September 1982


RecA protein of Escherichia coli has a third essential role in SOS mutator activity.
journal, June 1990


The Biochemical Requirements of DNA Polymerase V-mediated Translesion Synthesis Revisited
journal, August 2004

  • Fujii, Shingo; Gasser, Véronique; Fuchs, Robert P.
  • Journal of Molecular Biology, Vol. 341, Issue 2
  • DOI: 10.1016/j.jmb.2004.06.017

Biochemical basis for the essential genetic requirements of RecA and the  -clamp in Pol V activation
journal, August 2009

  • Fujii, S.; Fuchs, R. P.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 35
  • DOI: 10.1073/pnas.0905855106

RecA acts in trans to allow replication of damaged DNA by DNA polymerase V
journal, August 2006

  • Schlacher, Katharina; Cox, Michael M.; Woodgate, Roger
  • Nature, Vol. 442, Issue 7105
  • DOI: 10.1038/nature05042

The active form of DNA polymerase V is UmuD′2C–RecA–ATP
journal, July 2009

  • Jiang, Qingfei; Karata, Kiyonobu; Woodgate, Roger
  • Nature, Vol. 460, Issue 7253
  • DOI: 10.1038/nature08178

Translesion synthesis in Escherichia coli: Lessons from the NarI mutation hot spot
journal, July 2007


Translesion DNA Synthesis and Mutagenesis in Prokaryotes
journal, December 2013


Defining the position of the switches between replicative and bypass DNA polymerases
journal, October 2004


Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli
journal, November 2011

  • Gon, S.; Napolitano, R.; Rocha, W.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 48
  • DOI: 10.1073/pnas.1113664108

Pol V-Mediated Translesion Synthesis Elicits Localized Untargeted Mutagenesis during Post-replicative Gap Repair
journal, July 2018


Fate of DNA replication fork encountering a single DNA lesion during oriC plasmid DNA replication in vitro
journal, May 2003


Monitoring bypass of single replication-blocking lesions by damage avoidance in the Escherichia coli chromosome
journal, July 2012

  • Pagès, Vincent; Mazón, Gerard; Naiman, Karel
  • Nucleic Acids Research, Vol. 40, Issue 18
  • DOI: 10.1093/nar/gks675

Chronology in lesion tolerance gives priority to genetic variability
journal, March 2014

  • Naiman, K.; Philippin, G.; Fuchs, R. P.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 15
  • DOI: 10.1073/pnas.1321008111

DNA Damage-Induced Replication Fork Regression and Processing in Escherichia coli
journal, January 2003


Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites
journal, September 2011


A defect in homologous recombination leads to increased translesion synthesis in E. coli
journal, June 2016

  • Naiman, Karel; Pagès, Vincent; Fuchs, Robert P.
  • Nucleic Acids Research, Vol. 44, Issue 16
  • DOI: 10.1093/nar/gkw488

    Works referencing / citing this record:

    A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes
    journal, December 2019

    • Chang, Seungwoo; Naiman, Karel; Thrall, Elizabeth S.
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 51
    • DOI: 10.1073/pnas.1914485116