Repository logo

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

Accepted version

Change log


Georgakopoulos-Soares, Ilias 
Momen, Sophie E 
Jiricny, Josef 


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.



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, Polynucleotides, Repetitive Sequences, Nucleic Acid, Sequence Analysis, RNA, Transcription, Genetic

Journal Title

Nat Commun

Conference Name

Journal ISSN


Volume Title



Springer Science and Business Media LLC


All rights reserved
Cancer Research UK (23916)
Cancer Research UK (25274)
Cancer Research UK (CRUK) - C60100/A23916 [Nik-Zainal] Cancer Research UK (CRUK) - C60100/A25274 [Nik-Zainal]