The Mismatch-Binding Factor MutS? Can Mediate ATR Activation in Response to DNA Double-Strand Breaks

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F15%3A00455784" target="_blank" >RIV/68378050:_____/15:00455784 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.molcel.2015.06.026" target="_blank" >http://dx.doi.org/10.1016/j.molcel.2015.06.026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molcel.2015.06.026" target="_blank" >10.1016/j.molcel.2015.06.026</a>

Result language

angličtina

Original language name

The Mismatch-Binding Factor MutS? Can Mediate ATR Activation in Response to DNA Double-Strand Breaks

Original language description

Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase, a master regulator of DNA-damage response, is activated by RPA-coated single-stranded DNA (ssDNA) generated at stalled replication forks or DNA double-strand breaks (DSBs). Here, we identify the mismatch-binding protein MutS beta, a heterodimer of MSH2 and MSH3, as a key player in this process. MSH2 and MSH3 form a complex with ATR and its regulatory partner ATRIP, and their depletion compromises the formation of ATRIP foci and phosphorylation of ATR substrates in cells responding to replication-associated DSBs. Purified MutS beta binds to hairpin loop structures that persist in RPA-ssDNA complexes and promotes ATRIP recruitment. Mutations in the mismatch-binding domain of MSH3 abolish the binding of MutS beta to DNA hairpin loops and its ability to promote ATR activation by ssDNA. These results suggest that hairpin loops might form in ssDNA generated at sites of DNA damage and trigger ATR activation in a process medi

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

EB - Genetics and molecular biology

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

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

Name of the periodical

Molecular Cell

ISSN

1097-2765

e-ISSN

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Volume of the periodical

59

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

603-614

UT code for WoS article

000362457900011

EID of the result in the Scopus database

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