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DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells
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SYSNO ASEP 0567650 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells Author(s) Boleslavská, Barbora (UMG-J)
Oravetzová, Anna (UMG-J)
Shukla, Kaustubh (UMG-J)
Naščáková, Zuzana (UMG-J)
Ibini, O. N. (IN)
Hašanová, Zdeňka (UMG-J)
Andrš, Martin (UMG-J)
Kanagaraj, R. (IN)
Dobrovolná, Jana (UMG-J) RID
Janščák, Pavel (UMG-J) RIDNumber of authors 10 Source Title Nucleic Acids Research. - : Oxford University Press - ISSN 0305-1048
Roč. 50, č. 21 (2022), s. 12274-12290Number of pages 17 s. Language eng - English Country GB - United Kingdom Keywords common fragile sites ; dna-damage ; fork reversal ; biotin ligase ; rna helicase ; stress ; phase ; yeast ; ends ; p72 OECD category Biochemistry and molecular biology R&D Projects GA22-08294S GA ČR - Czech Science Foundation (CSF) GX21-22593X GA ČR - Czech Science Foundation (CSF) LTAUSA19096 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000893009700001 DOI 10.1093/nar/gkac1116 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2023 Electronic address https://academic.oup.com/nar/article/50/21/12274/6858780?login=true
Number of the records: 1