Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair
synthesis

J 2013

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

BURKOVICS, Peter, Marek ŠEBESTA, Alexandra SISÁKOVÁ, Nicolas PLAULT, Valeria SZUKACSOV et. al.

Basic information

Original name

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

Authors

BURKOVICS, Peter (348 Hungary, belonging to the institution), Marek ŠEBESTA (703 Slovakia, belonging to the institution), Alexandra SISÁKOVÁ (703 Slovakia, belonging to the institution), Nicolas PLAULT (250 France), Valeria SZUKACSOV (348 Hungary), Thomas ROBERT (250 France), Lajos PINTER (348 Hungary), María Victoria MARINI PALOMEQUE (858 Uruguay, belonging to the institution), Peter KOLESÁR (703 Slovakia, belonging to the institution), Lajos HARACSKA (348 Hungary), Serge GANGLOFF (250 France) and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

EMBO JOURNAL, NEW YORK, NATURE PUBLISHING GROUP, 2013, 0261-4189

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: 10.748

RIV identification code

RIV/00216224:14110/13:00066406

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/emboj.2013.9

UT WoS

000316468000014

Keywords in English

DNA repair synthesis; genome stability; PCNA SUMOylation; Srs2; SUMO interacting motif

Abstract

V originále

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Pol delta and Pol eta from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.

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

GA301/09/1917, research and development project

Name: Štěpení replikačních-rekombinačních DNA meziproduktů a jejich úloha při nestabilitě genomu

Investor: Czech Science Foundation

GD203/09/H046, research and development project

Name: Biochemie na rozcestí mezi in silico a in vitro

Investor: Czech Science Foundation

ME10048, research and development project

Name: Vliv post-translačních modifikací na DNA opravu a rekombinaci.

Investor: Ministry of Education, Youth and Sports of the CR, Research and Development Programme KONTAKT (ME)

Files attached

Role_of_PCNA.pdf

Request the author's version of the file

Citovat

BURKOVICS, Peter, Marek ŠEBESTA, Alexandra SISÁKOVÁ, Nicolas PLAULT, Valeria SZUKACSOV, Thomas ROBERT, Lajos PINTER, María Victoria MARINI PALOMEQUE, Peter KOLESÁR, Lajos HARACSKA, Serge GANGLOFF and Lumír KREJČÍ. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO JOURNAL. NEW YORK: NATURE PUBLISHING GROUP, 2013, vol. 32, No 5, p. 742-755. ISSN 0261-4189. Available from: https://dx.doi.org/10.1038/emboj.2013.9.

@article{1124592,
   author = {Burkovics, Peter and Šebesta, Marek and Sisáková, Alexandra and Plault, Nicolas and Szukacsov, Valeria and Robert, Thomas and Pinter, Lajos and Marini Palomeque, María Victoria and Kolesár, Peter and Haracska, Lajos and Gangloff, Serge and Krejčí, Lumír},
   article_location = {NEW YORK},
   article_number = {5},
   doi = {http://dx.doi.org/10.1038/emboj.2013.9},
   keywords = {DNA repair synthesis; genome stability; PCNA SUMOylation; Srs2; SUMO interacting motif},
   language = {eng},
   issn = {0261-4189},
   journal = {EMBO JOURNAL},
   title = {Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis},
   volume = {32},
   year = {2013}
}

TY  - JOUR
ID  - 1124592
AU  - Burkovics, Peter - Šebesta, Marek - Sisáková, Alexandra - Plault, Nicolas - Szukacsov, Valeria - Robert, Thomas - Pinter, Lajos - Marini Palomeque, María Victoria - Kolesár, Peter - Haracska, Lajos - Gangloff, Serge - Krejčí, Lumír
PY  - 2013
TI  - Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis
JF  - EMBO JOURNAL
VL  - 32
IS  - 5
SP  - 742-755
EP  - 742-755
PB  - NATURE PUBLISHING GROUP
SN  - 02614189
KW  - DNA repair synthesis
KW  - genome stability
KW  - PCNA SUMOylation
KW  - Srs2
KW  - SUMO interacting motif
N2  - Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Pol delta and Pol eta from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.
ER  -

BURKOVICS, Peter, Marek ŠEBESTA, Alexandra SISÁKOVÁ, Nicolas PLAULT, Valeria SZUKACSOV, Thomas ROBERT, Lajos PINTER, María Victoria MARINI PALOMEQUE, Peter KOLESÁR, Lajos HARACSKA, Serge GANGLOFF and Lumír KREJČÍ. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. \textit{EMBO JOURNAL}. NEW YORK: NATURE PUBLISHING GROUP, 2013, vol.~32, No~5, p.~742-755. ISSN~0261-4189. Available from: https://dx.doi.org/10.1038/emboj.2013.9.

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