Oxidative stress at telomeres triggers internal DNA loops, TRF1 dissociation, and TRF2-dependent R-loops.

ABSTRACT: Telomeres are the nucleoprotein structures at chromosome ends. Telomeres are particularly sensitive to oxidative stress, which can induce telomere damage, shortening, and premature cellular senescence. How oxidative damage influences telomere structure has not been defined. Here, we induce oxidative damage at telomeres using menadione, which damages mitochondria mimicking intrinsic oxidative stress. We find that oxidative stress induces at telomeres single-stranded DNA breaks, internal DNA loop structures, dissociation of the shelterin component TRF1, upregulation of TERRA long noncoding RNA, and increased DNA:RNA hybrid structures known as R-loops. R-loop formation is enhanced not only in cis at telomeres, which show increased TERRA transcription, but also in trans at telomeres at which T

SUBMITTER: Nguyen TT 

PROVIDER: S-EPMC11992676 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature