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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional repression accounts for RNA:DNA hybrids accumulation at DNA Double Strand breaks

ABSTRACT: RNA:DNA hybrids accumulate at the vicinity of DNA double-strand breaks (DSBs) and were shown to regulate homologous recombination repair. The mechanism responsible for the formation of these non-canonical RNA:DNA structures remains unclear although they were proposed to arise consequently to RNA Polymerase II or III loading followed by DSB-induced de novo transcription at the break site. Here, we found no evidence of RNA polymerases recruitment at DSBs. Rather, strand-specific R-loop mapping revealed that RNA:DNA hybrids are mainly generated at DSBs occurring in transcribing loci, from the hybridization of pre-existing RNA to the 3’ overhang left by DNA end resection. We further identified the H3K4me3 reader Spindlin 1 and the transcriptional regulator PAF1 as promoting RNA:DNA hybrid accumulation at DSBs, through their role in mediating transcriptional repression in cis to DSBs. Altogether, we provide evidence that RNA:DNA hybrids accumulate at DSBs occurring in transcribing loci as a result of DSB-induced transcriptional shut-down.

INSTRUMENT(S): NextSeq 500, NextSeq 2000

ORGANISM(S): Homo sapiens

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PROVIDER: E-MTAB-13197 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP168512

REPOSITORIES: biostudies-arrayexpress

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