XRCC1 prevents toxic PARP1 trapping during DNA base excision repair

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00544972" target="_blank" >RIV/68378050:_____/21:00544972 - isvavai.cz</a>

Result on the web

<a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00366-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS109727652100366X%3Fshowall%3Dtrue" target="_blank" >https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00366-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS109727652100366X%3Fshowall%3Dtrue</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molcel.2021.05.009" target="_blank" >10.1016/j.molcel.2021.05.009</a>

Result language

angličtina

Original language name

XRCC1 prevents toxic PARP1 trapping during DNA base excision repair

Original language description

Mammalian DNA base excision repair (BER) is accelerated by poly(ADP-ribose) polymerases (PARPs) and the scaffold protein XRCC1. PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. Here, we show that protein complexes containing DNA polymerase beta and DNA ligase III that are assembled by XRCC1 prevent excessive engagement and activity of PARP1 during BER. As a result, PARP1 becomes ´trapped´ on BER intermediates in XRCC1-deficient cells in a manner similar to that induced by PARP inhibitors, including in patient fibroblasts from XRCC1-mutated disease. This excessive PARP1 engagement and trapping renders BER intermediates inaccessible to enzymes such as DNA polymerase beta and impedes their repair. Consequently, PARP1 deletion rescues BER and resistance to base damage in XRCC1(-/-) cells. These data reveal excessive PARP1 engagement during BER as a threat to genome integrity and identify XRCC1 as an ´anti-trapper´ that prevents toxic PARP1 activity.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

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

1097-4164

Volume of the periodical

81

Issue of the periodical within the volume

14

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

3018-3030

UT code for WoS article

000675833000005

EID of the result in the Scopus database

—