Dataset Information

RNA Transcripts Serve as a Template for Double-Strand Break Repair in Human Cells

ABSTRACT: Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, emerging evidence suggests that RNA:DNA hybrids and transcripts near damaged sites can influence repair outcomes. However, a direct role for transcript RNA as a template during DSB repair in human cells is yet to be established. In this study, we designed fluorescent- and sequencing-based assays, which demonstrated that RNA-containing oligonucleotides and messenger RNA serve as templates to promote DSB repair. We conducted a CRISPR/Cas9-based genetic screen to identify factors that promote RNA-templated DSB repair (RT- DSBR), and of the candidate polymerases, we identified DNA polymerase-zeta (Polζ) as the potential reverse transcriptase that facilitates RT-DSBR. Furthermore, by analyzing sequencing data from cancer genomes, we identified the presence of whole intron deletions, a unique genomic scar reflective of RT- DSBR activity generated when spliced mRNA serves as the repair template. These findings highlight RT- DSBR as an alternative pathway for repairing DSBs in transcribed genes, with potential mutagenic consequences.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290535 | GEO | 2025/03/25

REPOSITORIES: GEO

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