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 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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Woo TT,Chuang CN,Higashide M,Shinohara A,Wang TF

doi

10.1093/nar/gkaa587

subject

Has Abstract

pub_date

2020-09-04 00:00:00

pages

8474-8489

issue

15

eissn

0305-1048

issn

1362-4962

pii

5870334

journal_volume

48

pub_type

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