{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Reijns MAM"],"funding":["Cancer Research UK","Medical Research Council","Blood Cancer UK","European Hematology Association","National Institute for Health Research (NIHR)","Wellcome Trust","Biotechnology and Biological Sciences Research Council","Academy of Medical Sciences"],"pagination":["623-631"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8866115"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["602(7898)"],"pubmed_abstract":["The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair<sup>1</sup>. In microorganisms, transcription has been demonstrated to be mutagenic<sup>2,3</sup>; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes<sup>4</sup>. Here we show that ID4-a cancer insertion-deletion (indel) mutation signature of unknown aetiology<sup>5</sup> characterized by short (2 to 5 base pair) deletions -is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activ"],"journal":["Nature"],"pubmed_title":["Signatures of TOP1 transcription-associated mutagenesis in cancer and germline."],"pmcid":["PMC8866115"],"funding_grant_id":["MC_UU_00007/11","MR/X013677/1","15047","19771","BB/J004243/1","MC_PC_14089","NF-SI-0617-10154","27589","27963","25514","AMS-CSF4-Church","MR/K001744/1","204802/Z/16/Z","MC_EX_MR/M009203/1","28640","NF-SI-0512-10113","MC_UU_00007/5","MC_UU_00009/2","RG69","CL-2010-13-007"],"pubmed_authors":["Williams TC","Chan GC","Williams E","Lopez-Bigas N","Culliford R","Sottoriva A","Maleady-Crowe F","Cornish AJ","Nadeu F","Lahnstein L","Hubbard TJP","Thorn S","Welland MJ","Palles C","Stuckey A","Caulfield MJ","Hamblin A","Mueller M","O'Donovan P","Frangou A","Ambrose JC","Scott RH","Tucci A","Jackson AP","Bleda M","Leigh SEA","Patch C","Thomas ERA","Stankovic T","Jones LJ","Arumugam P","Henderson S","Cross W","Gruber A","Murugaesu N","Reijns MAM","Leong IUS","Kousathanas A","Witkowska K","Tanguy M","Smith SC","Giess A","Schuh A","Rendon A","Perez-Gil D","Campo E","Wood H","Boustred CR","Siddiq A","Odhams CA","Wood SM","Houlston R","Savage K","Taylor Tavares AL","Bevers R","Fowler T","Pullinger J","Cornish A","Taylor MS","Caravagna G","Genomics England Research Consortium","Minneci F","Noyvert B","Ridout K","Elgar G","Sieghart A","Chubb D","Arnedo-Pac C","Parry DA","Graham T","Boyle S","Carroll P","Church D","Moutsianas L","Brittain H","Kasperaviciute D","Xiang H","Pereira MB","Aden K","Rogers T","Tomlinson I","Boardman-Pretty F","Kinnersley B","McEntagart M","Kayikci M","Thompson SR","Royo R","Jackson R","Lopez JF","Quirke P","Sosinsky A","Rios Szwed DO","Need AC","Sawant K","Wedge D","Nicholson MD","Colorectal Cancer Domain UK 100,000 Genomes Project","Hindshaw RL","Rahim T"],"additional_accession":[]},"is_claimable":false,"name":"Signatures of TOP1 transcription-associated mutagenesis in cancer and germline.","description":"The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair<sup>1</sup>. In microorganisms, transcription has been demonstrated to be mutagenic<sup>2,3</sup>; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes<sup>4</sup>. Here we show that ID4-a cancer insertion-deletion (indel) mutation signature of unknown aetiology<sup>5</sup> characterized by short (2 to 5 base pair) deletions -is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-04-08T17:58:18.65Z","creation":"2026-04-08T08:10:41.457Z"},"accession":"S-EPMC8866115","cross_references":{"pubmed":["35140396"],"doi":["10.1038/s41586-022-04403-y"]}}