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

journal contribution
posted on 2023-06-08, 06:33 authored by Karen M Lee, Suzanne Nizza, Thomas Hayes, Kirstin L Bass, Anja Irmisch, Jo Murray, Matthew J O'Connell
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.

History

Publication status

  • Published

Journal

Genetics

ISSN

0016-6731

Issue

4

Volume

175

Page range

1585-95

Pages

11.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Notes

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.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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