Saccharomyces Ku70, Mre11/Rad50, and RPA proteins regulate adaptation to G2/M arrest after DNA damage

Sang Eun Lee; J. Kent Moore; Allyson Holmes; Keiko Umezu; Richard D. Kolodner; James E. Haber

doi:10.1016/S0092-8674(00)81482-8

Saccharomyces Ku70, Mre11/Rad50, and RPA proteins regulate adaptation to G2/M arrest after DNA damage

Sang Eun Lee, J. Kent Moore, Allyson Holmes, Keiko Umezu, Richard D. Kolodner, James E. Haber

Research output: Contribution to journal › Article › peer-review

668 Scopus citations

Abstract

Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint. The effect of hdf1 results from its accelerated 5' to 3' degradation of the broken chromosome. Permanent arrest in hdf1 cells is suppressed by rad50 or mre11 deletions that retard this degradation. Wild-type HDF1 cells also become permanently arrested when they experience two unrepairable DSBs. Both DSB- induced arrest conditions are suppressed by a mutation in the single-strand binding protein, RPA. We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation.

Original language	English (US)
Pages (from-to)	399-409
Number of pages	11
Journal	Cell
Volume	94
Issue number	3
DOIs	https://doi.org/10.1016/S0092-8674(00)81482-8
State	Published - Aug 7 1998
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)81482-8

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title = "Saccharomyces Ku70, Mre11/Rad50, and RPA proteins regulate adaptation to G2/M arrest after DNA damage",

abstract = "Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint. The effect of hdf1 results from its accelerated 5' to 3' degradation of the broken chromosome. Permanent arrest in hdf1 cells is suppressed by rad50 or mre11 deletions that retard this degradation. Wild-type HDF1 cells also become permanently arrested when they experience two unrepairable DSBs. Both DSB- induced arrest conditions are suppressed by a mutation in the single-strand binding protein, RPA. We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation.",

author = "Lee, {Sang Eun} and Moore, {J. Kent} and Allyson Holmes and Keiko Umezu and Kolodner, {Richard D.} and Haber, {James E.}",

note = "Funding Information: We thank V. Zakian, W. Siede, and T. Weinert for providing strains and plasmids. We thank members of the Haber lab for many lively discussions. P. Wensink generously taught us to photograph cells. We are grateful to R. Sen, L. Davis, and S. Lovett for many helpful suggestions on the manuscript. This work was supported by Department of Energy grant ER91ER61235 and National Institutes of Health grant GM20056 to J. E. H. and National Institutes of Health grant GM50006 to R. D. K; S. E. L. is a Postdoctoral Fellow of the Leukemia Society of America. A. H. was supported in part by a United States Public Health Service Training Grant in Genetics, GM70122.",

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AU - Lee, Sang Eun

AU - Moore, J. Kent

AU - Holmes, Allyson

AU - Umezu, Keiko

AU - Kolodner, Richard D.

AU - Haber, James E.

N1 - Funding Information: We thank V. Zakian, W. Siede, and T. Weinert for providing strains and plasmids. We thank members of the Haber lab for many lively discussions. P. Wensink generously taught us to photograph cells. We are grateful to R. Sen, L. Davis, and S. Lovett for many helpful suggestions on the manuscript. This work was supported by Department of Energy grant ER91ER61235 and National Institutes of Health grant GM20056 to J. E. H. and National Institutes of Health grant GM50006 to R. D. K; S. E. L. is a Postdoctoral Fellow of the Leukemia Society of America. A. H. was supported in part by a United States Public Health Service Training Grant in Genetics, GM70122.

PY - 1998/8/7

Y1 - 1998/8/7

N2 - Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint. The effect of hdf1 results from its accelerated 5' to 3' degradation of the broken chromosome. Permanent arrest in hdf1 cells is suppressed by rad50 or mre11 deletions that retard this degradation. Wild-type HDF1 cells also become permanently arrested when they experience two unrepairable DSBs. Both DSB- induced arrest conditions are suppressed by a mutation in the single-strand binding protein, RPA. We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation.

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Saccharomyces Ku70, Mre11/Rad50, and RPA proteins regulate adaptation to G2/M arrest after DNA damage

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