A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage

Proceedings of the National Academy of Sciences of the United States of America - Tập 99 Số 26 - Trang 16934-16939 - 2002
Michael Chang1, Mohammed Bellaoui1,2, Charles Boone1,3, Grant W. Brown1,2
1Departments of Biochemistry and Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada M5S 1A8; and Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6
2Sloan-Kettering Institute, New York, NY
3Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada M5S 1A8;

Tóm tắt

We performed a systematic screen of the set of ≈5,000 viable Saccharomyces cerevisiae haploid gene deletion mutants and have identified 103 genes whose deletion causes sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). In total, 40 previously uncharacterized alkylation damage response genes were identified. Comparison with the set of genes known to be transcriptionally induced in response to MMS revealed surprisingly little overlap with those required for MMS resistance, indicating that transcriptional regulation plays little, if any, role in the response to MMS damage. Clustering of the MMS response genes on the basis of their cross-sensitivities to hydroxyurea, UV radiation, and ionizing radiation revealed a DNA damage core of genes required for responses to a broad range of DNA-damaging agents. Of particular significance, we identified a subset of genes that show a specific MMS response, displaying defects in S phase progression only in the presence of MMS. These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 99 Số 26

16934-16939

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