Transcription-dependent DNA double-strand breaks and human disease

Abstract

Accumulation of DNA damage in resting cells is an emerging cause of human disease. We identified a mechanism of DNA double-strand break (DSB) formation in non-replicating cells, which strictly depends on transcription. These transcriptional DSBs arise from the twinned processing of R-loops and topoisomerase I and may underlie neurological disorders and cancers.

Keywords

• dna double-strand break
• dna repair
• r-loop
• rna/dna hybrid
• senataxin
• tdp1
• xpf
• neurodegenerative disease
• cancer
• topoisomerase i
• transcription