{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Boleslavska B"],"funding":["Czech Academy of Sciences","Children with Cancer UK","Swiss National Science Foundation","The Ministry of Education, Youth and Sports","Charles University Grant Agency","Czech Science Foundation","CHILDREN with CANCER UK"],"pagination":["12274-12290"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9757067"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["50(21)"],"pubmed_abstract":["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."],"journal":["Nucleic acids research"],"pubmed_title":["DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells."],"pmcid":["PMC9757067"],"funding_grant_id":["310030_184716","LTAUSA19096","184716","L200522001","1332217","PGTaSFA\\100027","308119","310030","21-22593X","22-08294S","20-333"],"pubmed_authors":["Kanagaraj R","Janscak P","Andrs M","Ibini ON","Boleslavska B","Oravetzova A","Hasanova Z","Shukla K","Nascakova Z","Dobrovolna J"],"additional_accession":[]},"is_claimable":false,"name":"DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells.","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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-04-08T18:10:06.2Z","creation":"2025-04-19T10:47:10.934Z"},"accession":"S-EPMC9757067","cross_references":{"pubmed":["36453994"],"doi":["10.1093/nar/gkac1116"]}}