{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alagia A"],"funding":["Cancer Research UK","Medical Research Council"],"pagination":["7882"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12374970"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["DNA integrity is constantly challenged by both endogenous and exogenous damaging agents, resulting in various forms of damage. Failure to repair DNA accurately leads to genomic instability, a hallmark of cancer. Distinct pathways exist to repair different types of DNA damage. Double-strand breaks (DSBs) represent a particularly severe form of damage, due to the physical separation of DNA strands. The repair of DSBs requires the activity of RNA Polymerase II (RNAPII) and the generation of Damage-responsive transcripts (DARTs). Here we show that the RNA m5C-methyltransferase NSUN2 localises to DSBs in a transcription-dependent manner, where it binds to and methylates DARTs. The depletion of NSUN2 results in an accumulation of nascent primary DARTs around DSBs. Furthermore, we detect an RNA-dependent interaction between NSUN2 and DICER, which is stimulated by DNA damage. NSUN2 activity promotes DICER cleavage of DARTs-associated R-loops, which is required for efficient DNA repair. We report a role of the RNA m5C -methyltransferase NSUN2 within the RNA-dependent DNA damage response, highlighting its function as a DICER chaperone for the clearance of non-canonical substrates such as DARTs, thereby contributing to genomic integrity."],"journal":["Nature communications"],"pubmed_title":["NSUN2 facilitates DICER cleavage of DNA damage-associated R-loops to promote repair."],"pmcid":["PMC12374970"],"funding_grant_id":["BVR02590","BVR01170"],"pubmed_authors":["Gullerova M","Di Fazio A","Alagia A","Ajit K","Long Q"],"additional_accession":[]},"is_claimable":false,"name":"NSUN2 facilitates DICER cleavage of DNA damage-associated R-loops to promote repair.","description":"DNA integrity is constantly challenged by both endogenous and exogenous damaging agents, resulting in various forms of damage. Failure to repair DNA accurately leads to genomic instability, a hallmark of cancer. Distinct pathways exist to repair different types of DNA damage. Double-strand breaks (DSBs) represent a particularly severe form of damage, due to the physical separation of DNA strands. The repair of DSBs requires the activity of RNA Polymerase II (RNAPII) and the generation of Damage-responsive transcripts (DARTs). Here we show that the RNA m5C-methyltransferase NSUN2 localises to DSBs in a transcription-dependent manner, where it binds to and methylates DARTs. The depletion of NSUN2 results in an accumulation of nascent primary DARTs around DSBs. Furthermore, we detect an RNA-dependent interaction between NSUN2 and DICER, which is stimulated by DNA damage. NSUN2 activity promotes DICER cleavage of DARTs-associated R-loops, which is required for efficient DNA repair. We report a role of the RNA m5C -methyltransferase NSUN2 within the RNA-dependent DNA damage response, highlighting its function as a DICER chaperone for the clearance of non-canonical substrates such as DARTs, thereby contributing to genomic integrity.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-09T18:00:55.879Z","creation":"2026-04-08T01:08:59.393Z"},"accession":"S-EPMC12374970","cross_references":{"pubmed":["40849328"],"doi":["10.1038/s41467-025-63220-9"]}}