Cited by 55DNA Repair MechanismsFungal and yeast genetics researchBacterial Genetics and Biotechnology

Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast

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Pagès, Vincent, Santa Maria, Sergio R., Prakash, Louise, Prakash, Satya·2009·Genes & Development

Abstract

Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork stalled at the lesion site, the replication checkpoint presumably coordinates the action of lesion bypass processes with the replisome. However, it has remained unclear as to which of the lesion bypass processes—translesion synthesis (TLS) and/or template switching—depend on the activation of the replication checkpoint. Here we determine if the Mec1 kinase and the subunits of the checkpoint clamp and the clamp loader are required for TLS. We show that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the absence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase ζ-dependent TLS.

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  • An active checkpoint leads to Rev1 phosphorylation, possibly increasing TLS activity and reducing RPA-covered ssDNA, promoting checkpoint switch-off.

    “An active checkpoint leads to Rev1 phosphorylation [86,87], possibly increasing TLS activity and progressively reducing the amount of RPA-covered ssDNA, thus promoting the switch off of the checkpoint itself.”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [86]

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Authors
Pagès, V., Santa Maria, S. R., Prakash, L., & Prakash, S.
Affiliations
The University of Texas Medical Branch at Galveston (US)
Venue
Genes & Development
Published
2009-06-15
Volume
23
Issue
12
Pages
1438-1449
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2156568122
Cited by
55
References
43
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 6 · 2014: 1 · 2013: 4 · 2012: 7
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (CA107650)
  • National Cancer Institute (R01CA107650, CA107650)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
DNA damage, S-phase checkpoint, translesion synthesis, lesion bypass, Mec1 kinase, clamp loader, DNA polymerase zeta, nucleotide excision repair, template switching, replication fork stalling, yeast
MeSH terms
Y-Family DNA Polymerases, DNA Damage, DNA Repair, DNA Replication, DNA, Bacterial, Nucleotidyltransferases, Phosphoproteins, Phosphorylation, Saccharomyces cerevisiae, Ultraviolet Rays, Mutagenesis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing

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