Fanconi-Anemia-Associated Mutations Destabilize RAD51 Filaments and Impair Replication Fork Protection

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F17%3A00067614" target="_blank" >RIV/00159816:_____/17:00067614 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/17:00095172

Result on the web

<a href="http://dx.doi.org/10.1016/j.celrep.2017.09.062" target="_blank" >http://dx.doi.org/10.1016/j.celrep.2017.09.062</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2017.09.062" target="_blank" >10.1016/j.celrep.2017.09.062</a>

Result language

angličtina

Original language name

Fanconi-Anemia-Associated Mutations Destabilize RAD51 Filaments and Impair Replication Fork Protection

Original language description

Fanconi anemia (FA) is a genetic disorder characterized by a defect in DNA interstrand crosslink (ICL) repair, chromosomal instability, and a predisposition to cancer. Recently, two RAD51 mutations were reported to cause an FA-like phenotype. Despite the tight association of FA/HR proteins with replication fork (RF) stabilization during normal replication, it remains unknown how FA-associated RAD51 mutations affect replication beyond ICL lesions. Here, we report that these mutations fail to protect nascent DNA from MRE11-mediated degradation during RF stalling in Xenopus laevis egg extracts. Reconstitution of DNA protection in vitro revealed that the defect arises directly due to altered RAD51 properties. Both mutations induce pronounced structural changes and RAD51 filament destabilization that is not rescued by prevention of ATP hydrolysis due to aberrant ATP binding. Our results further interconnect the FA pathway with DNA replication and provide mechanistic insight into the role of RAD51 in recombination-independent mechanisms of genome maintenance.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

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

2017

Confidentiality

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

Name of the periodical

Cell Reports

ISSN

2211-1247

e-ISSN

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Volume of the periodical

21

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

8

Pages from-to

333-340

UT code for WoS article

000412686100005

EID of the result in the Scopus database

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