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

Abstract

AbstractTranscription-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 inDrosophila 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 inEscherichia coli, we studied the mutational signatures in flies with a deletion of the MMR genespellchecker1(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 inD. melanogaster. Based on the observed mutational strand-asymmetries, we conclude that TCR is still active withoutspel1. 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 inDrosophila melanogaster.