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Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces cerevisiae.
Genetics. 2018 01; 208(1):125-138.G

Abstract

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 sae2Δ, mre11Δ, exo1Δ, srs2Δ, rrm3Δ, and pol32Δ 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.

Authors+Show Affiliations

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.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.Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida 33620 kschmidt@usf.edu. Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29162625

Citation

Campos-Doerfler, Lillian, et al. "Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces Cerevisiae." Genetics, vol. 208, no. 1, 2018, pp. 125-138.
Campos-Doerfler L, Syed S, Schmidt KH. Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces cerevisiae. Genetics. 2018;208(1):125-138.
Campos-Doerfler, L., Syed, S., & Schmidt, K. H. (2018). Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces cerevisiae. Genetics, 208(1), 125-138. https://doi.org/10.1534/genetics.117.300545
Campos-Doerfler L, Syed S, Schmidt KH. Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces Cerevisiae. Genetics. 2018;208(1):125-138. PubMed PMID: 29162625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sgs1 Binding to Rad51 Stimulates Homology-Directed DNA Repair in Saccharomyces cerevisiae. AU - Campos-Doerfler,Lillian, AU - Syed,Salahuddin, AU - Schmidt,Kristina H, Y1 - 2017/11/21/ PY - 2017/05/23/received PY - 2017/11/16/accepted PY - 2017/11/23/pubmed PY - 2018/10/3/medline PY - 2017/11/23/entrez KW - DNA damage KW - DNA repair KW - Rad51 KW - Sgs1 KW - homologous recombination SP - 125 EP - 138 JF - Genetics JO - Genetics VL - 208 IS - 1 N2 - 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 sae2Δ, mre11Δ, exo1Δ, srs2Δ, rrm3Δ, and pol32Δ 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. SN - 1943-2631 UR - https://www.unboundmedicine.com/medline/citation/29162625/Sgs1_Binding_to_Rad51_Stimulates_Homology_Directed_DNA_Repair_in_Saccharomyces_cerevisiae_ L2 - http://www.genetics.org/cgi/pmidlookup?view=long&pmid=29162625 DB - PRIME DP - Unbound Medicine ER -