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.

Basic information

Original name

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

Authors

URULANGODI, Madhusoodanan (356 India), Marek ŠEBESTA (703 Slovakia, belonging to the institution), Demis MENOLFI (380 Italy), Barnabas SZAKAL (380 Italy), Julie SOLLIER (380 Italy), Alexandra SISÁKOVÁ (703 Slovakia, belonging to the institution), Lumír KREJČÍ (203 Czech Republic, belonging to the institution) and Dana BRANZEI (380 Italy)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 10.042

RIV identification code

RIV/00216224:14110/15:00081195

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000363002700009

Keywords in English

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

Abstract

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.

Links

GAP207/12/2323, research and development project

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

Investor: Czech Science Foundation

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

Citovat

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.

@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.

Detailed Information on Publication Record