Postreplication gaps at UV lesions are signals for checkpoint activation Journal Article
| Authors: | Callegari, A. J.; Clark, E.; Pneuman, A.; Kelly, T. J. |
| Article Title: | Postreplication gaps at UV lesions are signals for checkpoint activation |
| 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 Pol 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. |
| Keywords: | signal transduction; controlled study; nonhuman; dna polymerase; dna replication; ultraviolet radiation; animal cell; dna damage; cell cycle; cell cycle progression; cell cycle s phase; enzyme activation; pyrimidines; eukaryota; rna translation; eukaryotic cell; ultraviolet rays; genetic code; schizosaccharomyces; schizosaccharomycetaceae; schizosaccharomyces pombe; gene replication; dna, fungal; dna-directed dna polymerase; dna damage checkpoint; polζ; polη; polκ; rev1 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 107 |
| Issue: | 18 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2010-05-04 |
| Start Page: | 8219 |
| End Page: | 8224 |
| Language: | English |
| DOI: | 10.1073/pnas.1003449107 |
| PUBMED: | 20404181 |
| PROVIDER: | scopus |
| PMCID: | PMC2889594 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus" |
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