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

J 2015

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

URULANGODI, Madhusoodanan; Marek ŠEBESTA; Demis MENOLFI; Barnabas SZAKAL; Julie SOLLIER et. al.

Základní údaje

Originální název

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

Autoři

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

Vydání

Genes and Development, New York, Cold Spring Harbor Laboratory Press, 2015, 0890-9369

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 10.042

Kód RIV

RIV/00216224:14110/15:00081195

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1101/gad.265629.115

UT WoS

000363002700009

EID Scopus

2-s2.0-84943531043

Klíčová slova anglicky

DNA damage tolerance; replication; recombination; SUMO; genotoxic stress

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 11. 2015 12:28, Soňa Böhmová

Anotace

V originále

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.

Návaznosti

GAP207/12/2323, projekt VaV

Název: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

Citovat

URULANGODI, Madhusoodanan; Marek ŠEBESTA; Demis MENOLFI; Barnabas SZAKAL; Julie SOLLIER; Alexandra SISÁKOVÁ; Lumír KREJČÍ a 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, roč. 29, č. 19, s. 2067-2080. ISSN 0890-9369. Dostupné z: https://doi.org/10.1101/gad.265629.115.

@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 = {https://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 a 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, roč.~29, č.~19, s.~2067-2080. ISSN~0890-9369. Dostupné z: https://doi.org/10.1101/gad.265629.115.

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