Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts.

ABSTRACT: The mechanisms that underpin how insertions or deletions (indels) become fixed in DNA have primarily been ascribed to replication-related and/or double-strand break (DSB)-related processes. Here, we introduce a method to evaluate indels, orientating them relative to gene transcription. In so doing, we reveal a number of surprising findings: First, there is a transcriptional strand asymmetry in the distribution of mononucleotide repeat tracts in the reference human genome. Second, there is a strong transcriptional strand asymmetry of indels across 2,575 whole genome sequenced human cancers. We suggest that this is due to the activity of transcription-coupled nucleotide excision repair (TC-NER). Furthermore, TC-NER interacts with mismatch repair (MMR) under physiological conditions to produc

SUBMITTER: Georgakopoulos-Soares I 

PROVIDER: S-EPMC7181645 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature