Topoisomerase II contributes to DNA secondary structure-mediated double-stranded breaks.

ABSTRACT: DNA double-stranded breaks (DSBs) trigger human genome instability, therefore identifying what factors contribute to DSB induction is critical for our understanding of human disease etiology. Using an unbiased, genome-wide approach, we found that genomic regions with the ability to form highly stable DNA secondary structures are enriched for endogenous DSBs in human cells. Human genomic regions predicted to form non-B-form DNA induced gross chromosomal rearrangements in yeast and displayed high indel frequency in human genomes. The extent of instability in both analyses is in concordance with the structure forming ability of these regions. We also observed an enrichment of DNA secondary structure-prone sites overlapping transcription start sites (TSSs) and CCCTC-binding factor (CTCF) bindi

SUBMITTER: Szlachta K 

PROVIDER: S-EPMC7337936 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature