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Originally published as Genetics Published Articles Ahead of Print on July 29, 2007.

Genetics, Vol. 177, 47-61, September 2007, Copyright © 2007
doi:10.1534/genetics.107.077255

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Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe

Claire L. Dovey and Paul Russell1

Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 90237

1 Corresponding author: Department of Molecular Biology, The Scripps Research Institute, MB-3, 10550 North Torrey Pines Rd., La Jolla, CA 90237.
E-mail: prussell{at}scripps.edu

The faithful replication of the genome, coupled with the accurate repair of DNA damage, is essential for the maintenance of chromosomal integrity. The MMS22 gene of Saccharomyces cerevisiae plays an important but poorly understood role in preservation of genome integrity. Here we describe a novel gene in Schizosaccharomyces pombe that we propose is a highly diverged ortholog of MMS22. Fission yeast Mms22 functions in the recovery from replication-associated DNA damage. Loss of Mms22 results in the accumulation of spontaneous DNA damage in the S- and G2-phases of the cell cycle and elevated genomic instability. There are severe synthetic interactions involving mms22 and most of the homologous recombination proteins but not the structure-specific endonuclease Mus81-Eme1, which is required for survival of broken replication forks. Mms22 forms spontaneous nuclear foci and colocalizes with Rad22 in cells treated with camptothecin, suggesting that it has a direct role in repair of broken replication forks. Moreover, genetic interactions with components of the DNA replication fork suggest that Mms2 functions in the coordination of DNA synthesis following damage. We propose that Mms22 functions directly at the replication fork to maintain genomic integrity in a pathway involving Mus81-Eme1.




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T. M. Roberts, I. W. Zaidi, J. A. Vaisica, M. Peter, and G. W. Brown
Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase
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[Abstract] [Full Text] [PDF]




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