DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00567650" target="_blank" >RIV/68378050:_____/22:00567650 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/22:10456429
Result on the web
<a href="https://academic.oup.com/nar/article/50/21/12274/6858780?login=true" target="_blank" >https://academic.oup.com/nar/article/50/21/12274/6858780?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkac1116" target="_blank" >10.1093/nar/gkac1116</a>
Alternative languages
Result language
angličtina
Original language name
DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells
Original language description
R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81-LIG4-ELL pathway for resolution of R-loop-mediated transcription-replication conflicts, which may be involved in R-loop unwinding.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
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
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
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
50
Issue of the periodical within the volume
21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
17
Pages from-to
12274-12290
UT code for WoS article
000893009700001
EID of the result in the Scopus database
—