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Dual roles of yeast Rad51 N-terminal domain in repairing DNA double-strand breaks.

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 ?-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.

SUBMITTER: Woo TT 

PROVIDER: S-EPMC7470947 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Dual roles of yeast Rad51 N-terminal domain in repairing DNA double-strand breaks.

Woo Tai-Ting TT   Chuang Chi-Ning CN   Higashide Mika M   Shinohara Akira A   Wang Ting-Fang TF  

Nucleic acids research 20200901 15

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 auton  ...[more]

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