Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces cerevisiae

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Lillian Campos-Doerfler^1²  Kristina H. Schmidt^2²  Salahuddin Syed^1³ 

[1] Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612^2;Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida 33620;Graduate Program in Cell and Molecular Biology, University of South Florida, Tampa, Florida 33620^1

关键词: Sgs1;    Rad51;    homologous recombination;    DNA damage;    DNA repair;   

DOI  :  10.1534/genetics.117.300545

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

Accurate repair of DNA breaks is essential to maintain genome integrity and cellular fitness. Sgs1 , the sole member of the RecQ family of DNA helicases in Saccharomyces cerevisiae , is important for both early and late stages of homology-dependent repair. Its large number of physical and genetic interactions with DNA recombination, repair, and replication factors has established Sgs1 as a key player in the maintenance of genome integrity. To determine the significance of Sgs1 binding to the strand-exchange factor Rad51 , we have identified a single amino acid change at the C-terminal of the helicase core of Sgs1 that disrupts Rad51 binding. In contrast to an SGS1 deletion or a helicase-defective sgs1 allele, this new separation-of-function allele, sgs1 -FD , does not cause DNA damage hypersensitivity or genome instability, but exhibits negative and positive genetic interactions with sae2 Δ, mre11 Δ, exo1 Δ, srs2 Δ, rrm3 Δ, and pol32 Δ that are distinct from those of known sgs1 mutants. Our findings suggest that the Sgs1 - Rad51 interaction stimulates homologous recombination (HR). However, unlike sgs1 mutations, which impair the resection of DNA double-strand ends, negative genetic interactions of the sgs1 -FD allele are not suppressed by YKU70 deletion. We propose that the Sgs1 - Rad51 interaction stimulates HR by facilitating the formation of the presynaptic Rad51 filament, possibly by Sgs1 competing with single-stranded DNA for replication protein A binding during resection.

【 授权许可】

CC BY