J 2017

Role of PCNA and RFC in promoting Mus81-complex activity

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

Základní údaje

Originální název

Role of PCNA and RFC in promoting Mus81-complex activity

Autoři

SISÁKOVÁ, Alexandra (703 Slovensko, domácí), Veronika ALTMANNOVÁ (203 Česká republika, domácí), Marek ŠEBESTA (703 Slovensko, domácí) a Lumír KREJČÍ (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.770

Kód RIV

RIV/00216224:14110/17:00095209

Organizační jednotka

Lékařská fakulta

UT WoS

000412075900002

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 18. 3. 2018 16:47, Soňa Böhmová

Anotace

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.

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
MUNI/M/1894/2014, interní kód MU
Název: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression
Investor: Masarykova univerzita, Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression, INTERDISCIPLINARY - Mezioborové výzkumné projekty