Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00531327" target="_blank" >RIV/68378050:_____/20:00531327 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-020-17069-9" target="_blank" >https://www.nature.com/articles/s41467-020-17069-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-020-17069-9" target="_blank" >10.1038/s41467-020-17069-9</a>

Result language

angličtina

Original language name

Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair

Original language description

Neurodegeneration is a common hallmark of individuals with hereditary defects in DNA single-strand break repair, a process regulated by poly(ADP-ribose) metabolism. Recently, mutations in the ARH3 (ADPRHL2) hydrolase that removes ADP-ribose from proteins have been associated with neurodegenerative disease. Here, we show that ARH3-mutated patient cells accumulate mono(ADP-ribose) scars on core histones that are a molecular memory of recently repaired DNA single-strand breaks. We demonstrate that the ADP-ribose chromatin scars result in reduced endogenous levels of important chromatin modifications such as H3K9 acetylation, and that ARH3 patient cells exhibit measurable levels of deregulated transcription. Moreover, we show that the mono(ADP-ribose) scars are lost from the chromatin of ARH3-defective cells in the prolonged presence of PARP inhibition, and concomitantly that chromatin acetylation is restored to normal. Collectively, these data indicate that ARH3 can act as an eraser of ADP-ribose chromatin scars at sites of PARP activity during DNA single-strand break repair.

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

2020

Confidentiality

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

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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Volume of the periodical

11

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

3391

UT code for WoS article

000548309100010

EID of the result in the Scopus database

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