| URULANGODI, Madhusoodanan, Marek ŠEBESTA, Demis MENOLFI, Barnabas SZAKAL, Julie SOLLIER, Alexandra SISÁKOVÁ, Lumír KREJČÍ and Dana BRANZEI. Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication. Genes and Development. New York: Cold Spring Harbor Laboratory Press, 2015, vol. 29, No 19, p. 2067-2080. ISSN 0890-9369. Available from: https://dx.doi.org/10.1101/gad.265629.115. |
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@article{1317033,
author = {Urulangodi, Madhusoodanan and Šebesta, Marek and Menolfi, Demis and Szakal, Barnabas and Sollier, Julie and Sisáková, Alexandra and Krejčí, Lumír and Branzei, Dana},
article_location = {New York},
article_number = {19},
doi = {http://dx.doi.org/10.1101/gad.265629.115},
keywords = {DNA damage tolerance; replication; recombination; SUMO; genotoxic stress},
language = {eng},
issn = {0890-9369},
journal = {Genes and Development},
title = {Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication},
volume = {29},
year = {2015}
}
TY - JOUR
ID - 1317033
AU - Urulangodi, Madhusoodanan - Šebesta, Marek - Menolfi, Demis - Szakal, Barnabas - Sollier, Julie - Sisáková, Alexandra - Krejčí, Lumír - Branzei, Dana
PY - 2015
TI - Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication
JF - Genes and Development
VL - 29
IS - 19
SP - 2067-2080
EP - 2067-2080
PB - Cold Spring Harbor Laboratory Press
SN - 08909369
KW - DNA damage tolerance
KW - replication
KW - recombination
KW - SUMO
KW - genotoxic stress
N2 - 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.
ER -
URULANGODI, Madhusoodanan, Marek ŠEBESTA, Demis MENOLFI, Barnabas SZAKAL, Julie SOLLIER, Alexandra SISÁKOVÁ, Lumír KREJČÍ and Dana BRANZEI. Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication. \textit{Genes and Development}. New York: Cold Spring Harbor Laboratory Press, 2015, vol.~29, No~19, p.~2067-2080. ISSN~0890-9369. Available from: https://dx.doi.org/10.1101/gad.265629.115.
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