J 2017

Role of PCNA and RFC in promoting Mus81-complex activity

SISÁKOVÁ, Alexandra, Veronika ALTMANNOVÁ, Marek ŠEBESTA and Lumír KREJČÍ

Basic information

Original name

Role of PCNA and RFC in promoting Mus81-complex activity

Authors

SISÁKOVÁ, Alexandra (703 Slovakia, belonging to the institution), Veronika ALTMANNOVÁ (203 Czech Republic, belonging to the institution), Marek ŠEBESTA (703 Slovakia, belonging to the institution) and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

BMC BIOLOGY, LONDON, BIOMED CENTRAL LTD, 2017, 1741-7007

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.770

RIV identification code

RIV/00216224:14110/17:00095209

Organization unit

Faculty of Medicine

UT WoS

000412075900002

Keywords in English

Replication factor C; Proliferating cell nuclear antigen; Mus81 complex; Replication; Recombination

Tags

Tags

International impact, Reviewed
Změněno: 18/3/2018 16:47, Soňa Böhmová

Abstract

V originále

Background: Proper DNA replication is essential for faithful transmission of the genome. However, replication stress has serious impact on the integrity of the cell, leading to stalling or collapse of replication forks, and has been determined as a driving force of carcinogenesis. Mus81-Mms4 complex is a structure-specific endonuclease previously shown to be involved in processing of aberrant replication intermediates and promotes POLD3-dependent DNA synthesis via break-induced replication. However, how replication components might be involved in this process is not known. Results: Herein, we show the interaction and robust stimulation of Mus81-Mms4 nuclease activity by heteropentameric replication factor C(RFC) complex, the processivity factor of replicative DNA polymerases that is responsible for loading of proliferating cell nuclear antigen (PCNA) during DNA replication and repair. This stimulation is enhanced by RFC-dependent ATP hydrolysis and by PCNA loading on the DNA. Moreover, this stimulation is not specific to Rfc1, the largest of subunit of this complex, thus indicating that alternative clamp loaders may also play a role in the stimulation. We also observed a targeting of Mus81 by RFC to the nick-containing DNA substrate and we provide further evidence that indicates cooperation between Mus81 and the RFC complex in the repair of DNA lesions generated by various DNA-damaging agents. Conclusions: Identification of new interacting partners and modulators of Mus81-Mms4 nuclease, RFC, and PCNA imply the cooperation of these factors in resolution of stalled replication forks and branched DNA structures emanating from the restarted replication forks under conditions of replication stress.

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
MUNI/M/1894/2014, interní kód MU
Name: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects