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 (356 Indie), Marek ŠEBESTA (703 Slovensko, domácí), Demis MENOLFI (380 Itálie), Barnabas SZAKAL (380 Itálie), Julie SOLLIER (380 Itálie), Alexandra SISÁKOVÁ (703 Slovensko, domácí), Lumír KREJČÍ (203 Česká republika, domácí) a Dana BRANZEI (380 Itálie)

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

http://dx.doi.org/10.1101/gad.265629.115

UT WoS

000363002700009

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://dx.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 = {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 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://dx.doi.org/10.1101/gad.265629.115.

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