The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F16%3A00064015" target="_blank" >RIV/00159816:_____/16:00064015 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/16:00088204

Result on the web

<a href="http://dx.doi.org/10.1093/nar/gkw024" target="_blank" >http://dx.doi.org/10.1093/nar/gkw024</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkw024" target="_blank" >10.1093/nar/gkw024</a>

Result language

angličtina

Original language name

The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis

Original language description

Successful and accurate completion of the replication of damage-containing DNA requires mainly recombination and RAD18-dependent DNA damage tolerance pathways. RAD18 governs at least two distinct mechanisms: translesion synthesis (TLS) and template switching (TS)-dependent pathways. Whereas TS is mainly error-free, TLS can work in an error-prone manner and, as such, the regulation of these pathways requires tight control to prevent DNA errors and potentially oncogenic transformation and tumorigenesis. In humans, the PCNA-associated recombination inhibitor (PARI) protein has recently been shown to inhibit homologous recombination (HR) events. Here, we describe a biochemical mechanism in which PARI functions as an HR regulator after replication fork stalling and during double-strand break repair. In our reconstituted biochemical system, we show that PARI inhibits DNA repair synthesis during recombination events in a PCNA interaction-dependent way but independently of its UvrD-like helicase domain. In accordance, we demonstrate that PARI inhibits HR in vivo, and its knockdown suppresses the UV sensitivity of RAD18-depleted cells. Our data reveal a novel human regulatory mechanism that limits the extent of HR and represents a new potential target for anticancer therapy.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

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Volume of the periodical

44

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

3176-3189

UT code for WoS article

000375800200027

EID of the result in the Scopus database

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