Brc1-mediated DNA repair and damage tolerance

Sheedy, Daniel M, Dimitrova, Dora, Rankin, Jessica K, Bass, Kirstin L, Lee, Karen M, Tapia-Alveal, Claudia, Harvey, Susan H, Murray, Johanne and O'Connell, Matthew J (2005) Brc1-mediated DNA repair and damage tolerance. Genetics, 171 (2). pp. 457-468. ISSN 0016-6731

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The structural maintenance of chromosome (SMC) proteins are key elements in controlling chromosome dynamics. In eukaryotic cells, three essential SMC complexes have been defined: cohesin, condensin, and the Smc5/6 complex. The latter is essential for DNA damage responses; in its absence both repair and checkpoint responses fail. In fission yeast, the UV-C and ionizing radiation (IR) sensitivity of a specific hypomorphic allele encoding the Smc6 subunit, rad18-74 (renamed smc6-74), is suppressed by mild overexpression of a six-BRCT-domain protein, Brc1. Deletion of brc1 does not result in a hypersensitivity to UV-C or IR, and thus the function of Brc1 relative to the Smc5/6 complex has remained unclear. Here we show that brc1Delta cells are hypersensitive to a range of radiomimetic drugs that share the feature of creating lesions that are an impediment to the completion of DNA replication. Through a genetic analysis of brc1Delta epistasis and by defining genes required for Brc1 to suppress smc6-74, we find that Brc1 functions to promote recombination through a novel postreplication repair pathway and the structure-specific nucleases Slx1 and Mus81. Activation of this pathway through overproduction of Brc1 bypasses a repair defect in smc6-74, reestablishing resolution of lesions by recombination

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR0001 General
Depositing User: Johanne Murray
Date Deposited: 13 Nov 2012 14:52
Last Modified: 13 Nov 2012 14:52
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