Neuronal enhancers are hotspots for DNA single-strand break repair

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00544978" target="_blank" >RIV/68378050:_____/21:00544978 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41586-021-03468-5" target="_blank" >https://www.nature.com/articles/s41586-021-03468-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41586-021-03468-5" target="_blank" >10.1038/s41586-021-03468-5</a>

Result language

angličtina

Original language name

Neuronal enhancers are hotspots for DNA single-strand break repair

Original language description

Defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons(1,2). The cellular genome is subjected to a constant barrage of endogenous DNA damage, but surprisingly little is known about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here we show that post-mitotic neurons accumulate unexpectedly high levels of DNA single-strand breaks (SSBs) at specific sites within the genome. Genome-wide mapping reveals that SSBs are located within enhancers at or near CpG dinucleotides and sites of DNA demethylation. These SSBs are repaired by PARP1 and XRCC1-dependent mechanisms. Notably, deficiencies in XRCC1-dependent short-patch repair increase DNA repair synthesis at neuronal enhancers, whereas defects in long-patch repair reduce synthesis. The high levels of SSB repair in neuronal enhancers are therefore likely to be sustained by both short-patch and long-patch processes. These data provide the first evidence of site- and cell-type-specific SSB repair, revealing unexpected levels of localized and continuous DNA breakage in neurons. In addition, they suggest an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.

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

10601 - Cell 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

Nature

ISSN

0028-0836

e-ISSN

1476-4687

Volume of the periodical

593

Issue of the periodical within the volume

7859

Country of publishing house

GB - UNITED KINGDOM

Number of pages

5

Pages from-to

440-444

UT code for WoS article

000640199100002

EID of the result in the Scopus database

—