Abstract Transcription-coupled repair (TCR) removes base damage on the transcribed strand of a gene to ensure a quick resumption of transcription. Based on the absence of key enzymes for TCR and empirical evidence, TCR was thought to be missing in Drosophila melanogaster . The recent demonstration of TCR in S2 cells raises the question about the involved genes. Since the mismatch repair (MMR) pathway serves a central role in TCR, at least in Escherichia coli , we studied the mutational signatures in flies with a deletion of the MMR gene spellchecker1 ( spel1) , a MutS homolog. Whole-genome sequencing of mutation accumulation (MA) lines obtained 7,345 new single nucleotide variants (SNVs) and 5,672 short indel mutations, the largest data set from an MA study in D. melanogaster . Based on the observed mutational strand-asymmetries, we conclude that TCR is still active without spel1 . The operation of TCR is further confirmed by a negative association between mutation rate and gene expression. Surprisingly, the TCR signatures are detected for introns, but not for exons. We propose that an additional exon-specific repair pathway is masking the signature of TCR. This study presents the first step towards understanding the molecular basis of TCR in Drosophila melanogaster .

Transcription-coupled repair inDrosophila melanogasteris independent of the mismatch repair pathway