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dc.contributor.authorKumar, Niranjan
dc.contributor.authorTaneja, Arushi
dc.contributor.authorGhosh, Meenakshi
dc.contributor.authorRothweiler, Ulli
dc.contributor.authorSundaresan, Nagalingam Ravi
dc.contributor.authorSingh, Mahavir
dc.date.accessioned2024-09-03T07:50:12Z
dc.date.available2024-09-03T07:50:12Z
dc.date.issued2023-12-28
dc.description.abstracthe regulator of telomere elongation helicase 1 (RTEL1) plays roles in telomere DNA maintenance, DNA repair, and genome stability by dismantling D-loops and unwinding G-quadruplex structures. RTEL1 comprises a helicase domain, two tandem harmonin homology domains 1&2 (HHD1 and HHD2), and a Zn2+-binding RING domain. In vitro D-loop disassembly by RTEL1 is enhanced in the presence of replication protein A (RPA). However, the mechanism of RTEL1 recruitment at non-telomeric D-loops remains unknown. In this study, we have unravelled a direct physical interaction between RTEL1 and RPA. Under DNA damage conditions, we showed that RTEL1 and RPA colocalise in the cell. Coimmuno precipitation showed that RTEL1 and RPA interact, and the deletion of HHDs of RTEL1 significantly reduced this interaction. NMR chemical shift perturbations (CSPs) showed that RPA uses its 32C domain to interact with the HHD2 of RTEL1. Interestingly, HHD2 also interacted with DNA in the in vitro experiments. HHD2 structure was determined using X-ray crystallography, and NMR CSPs mapping revealed that both RPA 32C and DNA competitively bind to HHD2 on an overlapping surface. These results establish novel roles of accessory HHDs in RTEL1’s functions and provide mechanistic insights into the RPA-mediated recruitment of RTEL1 to DNA repair sites.en_US
dc.identifier.citationKumar, Taneja, Ghosh, Rothweiler, Sundaresan, Singh. Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites. Nucleic Acids Research (NAR). 2024;52(3):1450-1470en_US
dc.identifier.cristinIDFRIDAID 2250238
dc.identifier.doi10.1093/nar/gkad1208
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.urihttps://hdl.handle.net/10037/34505
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.relation.journalNucleic Acids Research (NAR)
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleHarmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sitesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)