Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts.
Amino Acid Motifs
Computational Biology
DNA Breaks, Double-Stranded
DNA Mutational Analysis
DNA Repair
DNA Replication
Gene Deletion
Gene Expression Regulation, Neoplastic
Genetic Variation
Genome, Human
Genomics
Humans
INDEL Mutation
Mutagenesis
Neoplasms
/ genetics
Polynucleotides
/ genetics
Repetitive Sequences, Nucleic Acid
Sequence Analysis, RNA
Transcription, Genetic
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
05
04
2019
accepted:
27
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
4
8
2020
Statut:
epublish
Résumé
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 produce strand bias. Finally, we show how insertions and deletions differ in their dependencies on these repair pathways. Our analytical approach reveals insights into the contribution of DNA repair towards indel mutagenesis in human cells.
Identifiants
pubmed: 32332764
doi: 10.1038/s41467-020-15901-w
pii: 10.1038/s41467-020-15901-w
pmc: PMC7181645
mid: EMS86141
doi:
Substances chimiques
Polynucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1980Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Swiss National Science Foundation
ID : 170267
Pays : Switzerland
Organisme : Cancer Research UK
ID : A23916
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A25274
Pays : United Kingdom
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