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Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase II.

Baldwin EL, Berger AC, Corbett AH, Osheroff N
Nucleic Acids Res. 2005 33 (3): 1021-30

PMID: 15718301 · PMCID: PMC549411 · DOI:10.1093/nar/gki246

The cleavage reaction of topoisomerase II, which creates double-stranded DNA breaks, plays a central role in both the cure and initiation of cancer. Therefore, it is important to understand the cellular processes that repair topoisomerase II-generated DNA damage. Using a genome-wide approach with Saccharomyces cerevisiae, we found that Deltamre11, Deltaxrs2, Deltarad50, Deltarad51, Deltarad52, Deltarad54, Deltarad55, Deltarad57 and Deltamms22 strains were hypersensitive to etoposide, a drug that specifically increases levels of topoisomerase II-mediated DNA breaks. These results confirm that the single-strand invasion pathway of homologous recombination is the major pathway that repairs topoisomerase II-induced DNA damage in yeast and also indicate an important role for Mms22p. Although Deltamms22 strains are sensitive to several DNA-damaging agents, little is known about the function of Mms22p. Deltamms22 cultures accumulate in G2/M, and display an abnormal cell cycle response to topoisomerase II-mediated DNA damage. MMS22 appears to function outside of the single-strand invasion pathway, but levels of etoposide-induced homologous recombination in Deltamms22 cells are lower than wild-type. MMS22 is epistatic with RTT101 and RTT107, genes that encode its protein binding partners. Finally, consistent with a role in DNA processes, Mms22p localizes to discrete nuclear foci, even in the absence of etoposide or its binding partners.

MeSH Terms (11)

Cell Cycle Cell Nucleus Cullin Proteins DNA Damage DNA Repair DNA Topoisomerases, Type II Etoposide Gene Deletion Recombination, Genetic Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins

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