Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication

Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Education. It includes Faculty of Medicine. Official publication website can be found on muni.cz.
Authors

URULANGODI Madhusoodanan ŠEBESTA Marek MENOLFI Demis SZAKAL Barnabas SOLLIER Julie SISÁKOVÁ Alexandra KREJČÍ Lumír BRANZEI Dana

Year of publication 2015
Type Article in Periodical
Magazine / Source Genes and Development
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1101/gad.265629.115
Field Genetics and molecular biology
Keywords DNA damage tolerance; replication; recombination; SUMO; genotoxic stress
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.