RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00588028" target="_blank" >RIV/68378050:_____/24:00588028 - isvavai.cz</a>
Alternative codes found
RIV/00209805:_____/24:00080129 RIV/00216208:11110/24:10483982 RIV/00216208:11310/24:10483982 RIV/00064165:_____/24:10483982
Result on the web
<a href="https://academic.oup.com/nar/article/52/13/7687/7694281?login=false" target="_blank" >https://academic.oup.com/nar/article/52/13/7687/7694281?login=false</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkae499" target="_blank" >10.1093/nar/gkae499</a>
Alternative languages
Result language
angličtina
Original language name
RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin
Original language description
RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, RAD18 has been implicated in homologous recombination. however, this function is incompletely understood. Here, we show that RAD18 is recruited to DNA lesions by monoubiquitination of histone H2A at K15 and counteracts accumulation of 53BP1. Super-resolution microscopy revealed that RAD18 localizes to the proximity of DNA double strand breaks and limits the distribution of 53BP1 to the peripheral chromatin nanodomains. Whereas auto-ubiquitination of RAD18 mediated by RAD6 inhibits its recruitment to DNA breaks, interaction with SLF1 promotes RAD18 accumulation at DNA breaks in the post-replicative chromatin by recognition of histone H4K20me0. Surprisingly, suppression of 53BP1 function by RAD18 is not involved in homologous recombination and rather leads to reduction of non-homologous end joining. Instead, we provide evidence that RAD18 promotes HR repair by recruiting the SMC5/6 complex to DNA breaks. Finally, we identified several new loss-of-function mutations in RAD18 in cancer patients suggesting that RAD18 could be involved in cancer development.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
52
Issue of the periodical within the volume
13
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
7687-7703
UT code for WoS article
001247647900001
EID of the result in the Scopus database
2-s2.0-85199398767