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SISÁKOVÁ, Alexandra, Veronika ALTMANNOVÁ, Marek ŠEBESTA and Lumír KREJČÍ. Role of PCNA and RFC in promoting Mus81-complex activity. BMC BIOLOGY. LONDON: BIOMED CENTRAL LTD, 2017, vol. 15, No 90, p. 1-17. ISSN 1741-7007. Available from: https://dx.doi.org/10.1186/s12915-017-0429-8.
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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
Original language English
Type of outcome Article in a journal
Field of Study 10600 1.6 Biological sciences
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 5.770
RIV identification code RIV/00216224:14110/17:00095209
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1186/s12915-017-0429-8
UT WoS 000412075900002
Keywords in English Replication factor C; Proliferating cell nuclear antigen; Mus81 complex; Replication; Recombination
Tags EL OK, podil
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 18/3/2018 16:47.
Abstract
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 projectName: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I
Investor: Czech Science Foundation
GA13-26629S, research and development projectName: SUMO a stability genomu
Investor: Czech Science Foundation
MUNI/M/1894/2014, interní kód MUName: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
Displayed: 30/4/2024 22:14