MutS beta regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00557103" target="_blank" >RIV/68378050:_____/22:00557103 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2211124722003503?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124722003503?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2022.110602" target="_blank" >10.1016/j.celrep.2022.110602</a>

Result language

angličtina

Original language name

MutS beta regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells

Original language description

Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed ´alternative lengthening of telomeres´ (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutS beta, a heterodimer of MSH2 and MSH3 subunits, is enriched at telomeres in ALT cancer cells, where it prevents the accumulation of telomeric G-quadruplex (G4) structures and R-loops. Cells depleted of MSH3 display increased incidence of R-loop-dependent telomere fragility and accumulation of telomeric C-circles. We also demonstrate that purified MutS beta recognizes and destabilizes G4 structures in vitro. These data suggest that MutS beta destabilizes G4 structures in ALT telomeres to regulate TERRA R-loops, which is a prerequisite for maintenance of telomere integrity during ALT.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

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

2211-1247

Volume of the periodical

39

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

19

Pages from-to

110602

UT code for WoS article

000785983000004

EID of the result in the Scopus database

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