Unloading of homologous recombination factors is required for
restoring double-stranded DNA at damage repair loci

J 2017

Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci

VASIANOVICH, Yulia, Veronika ALTMANNOVÁ, Oleksii KOTENKO, Matthew D. NEWTON, Lumír KREJČÍ et. al.

Basic information

Original name

Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci

Authors

VASIANOVICH, Yulia (826 United Kingdom of Great Britain and Northern Ireland), Veronika ALTMANNOVÁ (203 Czech Republic, belonging to the institution), Oleksii KOTENKO (826 United Kingdom of Great Britain and Northern Ireland), Matthew D. NEWTON (826 United Kingdom of Great Britain and Northern Ireland), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and Svetlana MAKOVETS (826 United Kingdom of Great Britain and Northern Ireland)

Edition

EMBO Journal, Hoboken, Wiley-Blackwell, 2017, 0261-4189

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 10.557

RIV identification code

RIV/00216224:14110/17:00094600

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.15252/embj.201694628

UT WoS

000393317800008

Keywords in English

DNA resynthesis; PCNA; Rad51; recombination machinery; Srs2

Abstract

V originále

Cells use homology-dependent DNA repair to mend chromosome breaks and restore broken replication forks, thereby ensuring genome stability and cell survival. DNA break repair via homologybased mechanisms involves nuclease-dependent DNA end resection, which generates long tracts of single-stranded DNA required for checkpoint activation and loading of homologous recombination proteins Rad52/51/55/57. While recruitment of the homologous recombination machinery is well characterized, it is not known how its presence at repair loci is coordinated with downstream resynthesis of resected DNA. We show that Rad51 inhibits recruitment of proliferating cell nuclear antigen (PCNA), the platform for assembly of the DNA replication machinery, and that unloading of Rad51 by Srs2 helicase is required for efficient PCNA loading and restoration of resected DNA. As a result, srs2D mutants are deficient in DNA repair correlating with extensive DNA processing, but this defect in srs2D mutants can be suppressed by inactivation of the resection nuclease Exo1. We propose a model in which during re-synthesis of resected DNA, the replication machinery must catch up with the preceding processing nucleases, in order to close the single-stranded gap and terminate further resection.

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

VASIANOVICH, Yulia, Veronika ALTMANNOVÁ, Oleksii KOTENKO, Matthew D. NEWTON, Lumír KREJČÍ and Svetlana MAKOVETS. Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci. EMBO Journal. Hoboken: Wiley-Blackwell, 2017, vol. 36, No 2, p. 213-231. ISSN 0261-4189. Available from: https://dx.doi.org/10.15252/embj.201694628.

@article{1367106,
   author = {Vasianovich, Yulia and Altmannová, Veronika and Kotenko, Oleksii and Newton, Matthew D. and Krejčí, Lumír and Makovets, Svetlana},
   article_location = {Hoboken},
   article_number = {2},
   doi = {http://dx.doi.org/10.15252/embj.201694628},
   keywords = {DNA resynthesis; PCNA; Rad51; recombination machinery; Srs2},
   language = {eng},
   issn = {0261-4189},
   journal = {EMBO Journal},
   title = {Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci},
   volume = {36},
   year = {2017}
}

TY  - JOUR
ID  - 1367106
AU  - Vasianovich, Yulia - Altmannová, Veronika - Kotenko, Oleksii - Newton, Matthew D. - Krejčí, Lumír - Makovets, Svetlana
PY  - 2017
TI  - Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci
JF  - EMBO Journal
VL  - 36
IS  - 2
SP  - 213-231
EP  - 213-231
PB  - Wiley-Blackwell
SN  - 02614189
KW  - DNA resynthesis
KW  - PCNA
KW  - Rad51
KW  - recombination machinery
KW  - Srs2
N2  - Cells use homology-dependent DNA repair to mend chromosome breaks and restore broken replication forks, thereby ensuring genome stability and cell survival. DNA break repair via homologybased mechanisms involves nuclease-dependent DNA end resection, which generates long tracts of single-stranded DNA required for checkpoint activation and loading of homologous recombination proteins Rad52/51/55/57. While recruitment of the homologous recombination machinery is well characterized, it is not known how its presence at repair loci is coordinated with downstream resynthesis of resected DNA. We show that Rad51 inhibits recruitment of proliferating cell nuclear antigen (PCNA), the platform for assembly of the DNA replication machinery, and that unloading of Rad51 by Srs2 helicase is required for efficient PCNA loading and restoration of resected DNA. As a result, srs2D mutants are deficient in DNA repair correlating with extensive DNA processing, but this defect in srs2D mutants can be suppressed by inactivation of the resection nuclease Exo1. We propose a model in which during re-synthesis of resected DNA, the replication machinery must catch up with the preceding processing nucleases, in order to close the single-stranded gap and terminate further resection.
ER  -

VASIANOVICH, Yulia, Veronika ALTMANNOVÁ, Oleksii KOTENKO, Matthew D. NEWTON, Lumír KREJČÍ and Svetlana MAKOVETS. Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci. \textit{EMBO Journal}. Hoboken: Wiley-Blackwell, 2017, vol.~36, No~2, p.~213-231. ISSN~0261-4189. Available from: https://dx.doi.org/10.15252/embj.201694628.

Detailed Information on Publication Record