Signatures of TOP1 transcription-associated mutagenesis in cancer and germline.

ABSTRACT: The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair¹. In microorganisms, transcription has been demonstrated to be mutagenic^2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes⁴. Here we show that ID4-a cancer insertion-deletion (indel) mutation signature of unknown aetiology⁵ 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

SUBMITTER: Reijns MAM 

PROVIDER: S-EPMC8866115 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature