RRC ID 74183
Author Woo TT, Chuang CN, Higashide M, Shinohara A, Wang TF.
Title Dual roles of yeast Rad51 N-terminal domain in repairing DNA double-strand breaks.
Journal Nucleic Acids Res
Abstract Highly toxic DNA double-strand breaks (DSBs) readily trigger the DNA damage response (DDR) in cells, which delays cell cycle progression to ensure proper DSB repair. In Saccharomyces cerevisiae, mitotic S phase (20-30 min) is lengthened upon DNA damage. During meiosis, Spo11-induced DSB onset and repair lasts up to 5 h. We report that the NH2-terminal domain (NTD; residues 1-66) of Rad51 has dual functions for repairing DSBs during vegetative growth and meiosis. Firstly, Rad51-NTD exhibits autonomous expression-enhancing activity for high-level production of native Rad51 and when fused to exogenous β-galactosidase in vivo. Secondly, Rad51-NTD is an S/T-Q cluster domain (SCD) harboring three putative Mec1/Tel1 target sites. Mec1/Tel1-dependent phosphorylation antagonizes the proteasomal degradation pathway, increasing the half-life of Rad51 from ∼30 min to ≥180 min. Our results evidence a direct link between homologous recombination and DDR modulated by Rad51 homeostasis.
Volume 48(15)
Pages 8474-8489
Published 2020-9-4
DOI 10.1093/nar/gkaa587
PII 5870334
PMID 32652040
PMC PMC7470947
MeSH DNA Breaks, Double-Stranded* DNA Damage / genetics DNA Repair / genetics DNA-Binding Proteins / genetics Endodeoxyribonucleases / genetics* Gene Expression Regulation, Fungal / genetics Intracellular Signaling Peptides and Proteins / genetics Meiosis / genetics* Phosphorylation / genetics Proteasome Endopeptidase Complex / genetics Protein Domains / genetics Protein Serine-Threonine Kinases / genetics Proteolysis Rad51 Recombinase / genetics* Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / genetics* beta-Galactosidase / genetics
IF 11.502