Cited by 54DNA Repair MechanismsFungal and yeast genetics researchMicrotubule and mitosis dynamics

Postreplication gaps at UV lesions are signals for checkpoint activation

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Callegari, A. John, Clark, Emily, Pneuman, Amanda, Kelly, Thomas J.·2010·Proceedings of the National Academy of Sciences

Abstract

Exposure of eukaryotic cells to UV light induces a checkpoint response that delays cell-cycle progression after cells enter S phase. It has been hypothesized that this checkpoint response provides time for repair by signaling the presence of structures generated when the replication fork encounters UV-induced DNA damage. To gain insight into the nature of the signaling structures, we used time-lapse microscopy to determine the effects of deficiencies in translesion DNA polymerases on the checkpoint response of the fission yeast Schizosaccharomyces pombe . We found that disruption of the genes encoding translesion DNA polymerases Polκ and Polη significantly prolonged the checkpoint response, indicating that the substrates of these enzymes are signals for checkpoint activation. Surprisingly, we found no evidence that the translesion polymerases Rev1 and Polζ repair structures that are recognized by the checkpoint despite their role in maintaining viability after UV irradiation. Quantitative flow cytometry revealed that cells lacking translesion polymerases replicate UV-damaged DNA at the same rate at WT cells, indicating that the enhanced checkpoint response of cells lacking Polκ and Polη is not the result of stalled replication forks. These observations support a model in which postreplication DNA gaps with unrepaired UV lesions in the template strand act both as substrates for translesion polymerases and as signals for checkpoint activation.

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Crossref · 10.1073/pnas.1003449107

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Authors
Callegari, A. J., Clark, E., Pneuman, A., & Kelly, T. J.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Venue
Proceedings of the National Academy of Sciences
Published
2010-04-19
Volume
107
Issue
18
Pages
8219-8224
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1996421216
Cited by
54
References
41
Citations by year
2026: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 9 · 2012: 5
FWCI
2.73
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM050806)
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 › Cell Biology › Microtubule and mitosis dynamics
Keywords
UV-induced DNA damage, DNA damage checkpoint, translesion DNA polymerases, Rev1, replication fork stalling, S-phase checkpoint, Schizosaccharomyces pombe, DNA repair, checkpoint signaling
MeSH terms
Y-Family DNA Polymerases, Cell Cycle, DNA Damage, DNA-Directed DNA Polymerase, DNA Replication, DNA, Fungal, Pyrimidines, Schizosaccharomyces, Ultraviolet Rays

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