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Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function
journal contribution
posted on 2023-06-07, 14:41 authored by Karen M Lee, Suzanne Nizza, Thomas Hayes, Kirstin L Bass, Anja Irmisch, Jo Murray, Matthew J O'ConnellSmc5/6 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 postreplication repair (PRR) 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 PRR. 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, although 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.
History
Publication status
- Published
File Version
- Published version
Journal
GeneticsISSN
0016-6731Publisher
Genetics Society of AmericaExternal DOI
Issue
4Volume
175Page range
1585-1595Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2008-07-29First Compliant Deposit (FCD) Date
2018-05-11Usage metrics
Categories
No categories selectedKeywords
Base Sequence Cell Cycle Proteins/*genetics/*metabolism Chromosomal ProteinsNon-Histone/*genetics/*metabolism DNA Repair/genetics DNAFungal/genetics DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics/metabolism Exodeoxyribonucleases/genetics/metabolism GenesFungal Mutation RecombinationGenetic Schizosaccharomyces/*genetics/growth & development/*metabolism Schizosaccharomyces pombe Proteins/*genetics/*metabolism
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