title: Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function.
abstract: 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 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.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lee
authors.forename: Suzanne
authors.initials: S
authors.lastname: Nizza
authors.forename: Thomas
authors.initials: T
authors.lastname: Hayes
authors.forename: Kirstin L
authors.initials: KL
authors.lastname: Bass
authors.forename: Anja
authors.initials: A
authors.lastname: Irmisch
authors.forename: Johanne M
authors.initials: JM
authors.lastname: Murray
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: O'Connell
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D009154:Mutation; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C511286:Brc1 protein, S pombe; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; C486628:Smc5 protein, S pombe; C486630:smc6 protein, S pombe; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; C480729:Apn2 protein, S pombe; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase