Brc1-mediated rescue of Smc5/6 deficiency; requirement for multiple nucleases and a novel rad18 function

Lee, Karen M, Nizza, Suzanne, Hayes, Thomas, Bass, Kirstin L, Irmisch, Anja, Murray, Johanne M and O'Connell, Matthew J (2007) Brc1-mediated rescue of Smc5/6 deficiency; requirement for multiple nucleases and a novel rad18 function. Genetics, 175 (4). pp. 1585-95. ISSN 0016-6731

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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.

Item Type: Article
Additional Information: 30% contribution. JM provided data for figs 4,5 and co-authored paper as part of a long-standing collaboration with MO'C, New York. We also contributed the biochemistry to back up the genetics, which was critical for publication. First demonstration of a role for Rhp18RAD18 outside ubiquitination of PCNA and post-replication repair.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Johanne Murray
Date Deposited: 06 Feb 2012 20:31
Last Modified: 30 Nov 2012 17:07
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