Cited by 282DNA Repair MechanismsUbiquitin and proteasome pathwaysFungal and yeast genetics research

The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase

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Karras, Georgios I., Jentsch, Stefan·2010·Cell

Abstract

Damaged DNA templates provide an obstacle to the replication fork and can cause genome instability. In eukaryotes, tolerance to damaged DNA is mediated largely by the RAD6 pathway involving ubiquitylation of the DNA polymerase processivity factor PCNA. Whereas monoubiquitylation of PCNA mediates error-prone translesion synthesis (TLS), polyubiquitylation triggers an error-free pathway. Both branches of this pathway are believed to occur in S phase in order to ensure replication completion. However, we found that limiting TLS or the error-free pathway to the G2/M phase of the cell-cycle efficiently promote lesion tolerance. Thus, our findings indicate that both branches of the DNA damage tolerance pathway operate effectively after chromosomal replication, outside S phase. We therefore propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks.

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Crossref · 10.1016/j.cell.2010.02.028

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  • In these conditions, repair may not be completed and ssDNA extension may both activate the checkpoint and channel the problematic lesion to another repair pathway such as recombination.

    “In these conditions, repair may not be completed and the extension of the ssDNA region may meet two purposes: activating the checkpoint response and channeling the problematic lesion to a different repair pathway (e.g., recombination) [66–68].”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [66]

  • S phase can be completed without PRR, but gapped replicated DNA must be refilled by PRR in G2 for cell survival.

    “In fact, S phase can be completed in the absence of PRR, but the gapped replicated DNA needs to be refilled by PRR in G2 in order to warrant cell survival [66,67].”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [66]

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Authors
Karras, G. I., & Jentsch, S.
Affiliations
  • Max Planck Institute of Biochemistry (DE)
  • Max Planck Society (DE)
Corresponding author
Jentsch, Stefan
Venue
Cell
Publisher
Elsevier BV
Published
2010-04
Volume
141
Issue
2
Pages
255-267
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2059788298
Cited by
282
References
96
Citations by year
2026: 7 · 2025: 9 · 2024: 2 · 2023: 7 · 2022: 9 · 2021: 12 · 2020: 20 · 2019: 20 · 2018: 17 · 2017: 17 · 2016: 27 · 2015: 20 · 2014: 21 · 2013: 24 · 2012: 23
FWCI
12.24
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
DNA damage tolerance, translesion synthesis, G2/M phase, S phase, replication fork restart, single-stranded DNA gaps, genomic instability, DNA polymerase processivity
MeSH terms
DNA Damage, DNA Repair, DNA Replication, DNA Helicases, Saccharomyces cerevisiae, S Phase, Proliferating Cell Nuclear Antigen, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes, RecQ Helicases, Metabolic Networks and Pathways, Ubiquitination

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