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Molecular and Cellular Biology, August 2004, p. 7082-7090, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.7082-7090.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mrc1 Is Required for Sister Chromatid Cohesion To Aid in Recombination Repair of Spontaneous Damage

Hong Xu,1 Charles Boone,1 and Hannah L. Klein2*

Banting and Best Department of Medical Research and Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, and University of Toronto, Toronto, Ontario M5G 1L6, Canada,1 Department of Biochemistry, New York University School of Medicine, and Kaplan Comprehensive Cancer Center, NYU Medical Center, New York, New York 100162

Received 31 March 2004/ Returned for modification 29 April 2004/ Accepted 6 May 2004

The SRS2 gene of Saccharomyces cerevisiae encoding a 3'->5' DNA helicase is part of the postreplication repair pathway and functions to ensure proper repair of DNA damage arising during DNA replication through pathways that do not involve homologous recombination. Through a synthetic gene array analysis, genes that are essential when Srs2 is absent have been identified. Among these are MRC1, TOF1, and CSM3, which mediate the intra-S checkpoint response. srs2{Delta} mrc1{Delta} synthetic lethality is due to inappropriate recombination, as the lethality can be suppressed by genetic elimination of homologous recombination. srs2{Delta} mrc1{Delta} synthetic lethality is dependent on the role of Mrc1 in DNA replication but independent of the role of Mrc1 in a DNA damage checkpoint response. mrc1{Delta}, tof1{Delta} and csm3{Delta} mutants have sister chromatid cohesion defects, implicating sister chromatid cohesion established at the replication fork as an important factor in promoting repair of stalled replication forks through gap repair.

* Corresponding author. Mailing address: Department of Biochemistry, NYU Medical Center, 550 First Ave., New York, NY 10016. Phone: (212) 263-5778. Fax: (212) 263-8166. E-mail: hannah.klein{at}med.nyu.edu.

Molecular and Cellular Biology, August 2004, p. 7082-7090, Vol. 24, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.16.7082-7090.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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