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doi:10.1534/genetics.106.067801
A more recent version of this article appeared on April 1, 2007.
REGULAR RESEARCH PAPERS |
Brc1-mediated rescue of Smc5/6 deficiency; requirement for multiple nucleases and a novel Rad18 function
Karen Lee 1, Suzanne Nizza 1, Thomas Hayes 1, Kirstin Bass 1, Anja Irmish 2, Johanne Murray 2 and Matthew O'Connell 1*
1 Mount Sinai School of Medicine
2 Genome Damage and Stability Centre
* To whom correspondence should be addressed. E-mail: matthew.oconnell{at}mssm.edu.
Submitted on November 3, 2006
Revised on November 30, 2006
Accepted on 24 January 2007
Smc5/6 is a Structural Maintenance of Chromosomes complex, related to the cohesin and condensin complexes. Recent studies implicate Smc5/6 as being essential for homologous recombination. Each gene is essential, but hypomorphic alleles are defective in the repair of a diverse array of lesions. A particular allele of smc6 (smc6-74) is suppressed by overexpression of Brc1, a six-BRCT domain protein that is required for DNA repair during S-phase. This suppression requires the post-replication repair protein Rhp18, and the structure-specific endonucleases Slx1/4 and Mus81/Eme1. However, we show here that the contribution of Rhp18 is via a novel pathway that is independent of PCNA ubiquitination and post-replication repair. Moreover, we identify Exo1 as an additional nuclease required for Brc1-mediated suppression of smc6-74, independent of mismatch repair. Further, the Apn2 endonuclease is required for the viability of smc6 mutants without extrinsic DNA damage, though this is not due to a defect in base excision repair. Several nucleotide excision repair genes are similarly shown to ensure viability of smc6 mutants. The requirement for excision factors for the viability of smc6 mutants is consistent with an inability to respond to spontaneous lesions by Smc5/6-dependent recombination.
Key Words: Brc1, DNA repair, Rad18, Smc5/6, endonuclease
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