Abstract:
:Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage bypass is enabled at replication stress sites remained puzzling. Here we uncovered that the conserved SUMO-like domain-containing Saccharomyces cerevisiae protein Esc2 facilitates recombination-mediated DNA damage tolerance by allowing optimal recruitment of the Rad51 recombinase specifically at sites of perturbed replication. Mechanistically, Esc2 binds stalled replication forks and counteracts the anti-recombinase Srs2 helicase via a two-faceted mechanism involving chromatin recruitment and turnover of Srs2. Importantly, point mutations in the SUMO-like domains of Esc2 that reduce its interaction with Srs2 cause suboptimal levels of Rad51 recruitment at damaged replication forks. In conclusion, our results reveal how recombination-mediated DNA damage tolerance is locally enabled at sites of replication stress and globally prevented at undamaged replicating chromosomes.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Urulangodi M,Sebesta M,Menolfi D,Szakal B,Sollier J,Sisakova A,Krejci L,Branzei Ddoi
10.1101/gad.265629.115subject
Has Abstractpub_date
2015-10-01 00:00:00pages
2067-80issue
19eissn
0890-9369issn
1549-5477pii
29/19/2067journal_volume
29pub_type
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