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RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence
Activation of RAS oncogenes in normal cells triggers a stable cell cycle arrest known as RAS-induced senescence (RIS), marked by persistent DNA damage and extensive epigenetic remodeling. Although bypassing RIS promotes tumorigenesis, the molecular mechanisms underlying this transition remain poorly defined. Here, we demonstrate that RIS cells accumulate high levels of R-loops-three-stranded DNA-RNA hybrids-that frequently co-localize with DNA G-quadruplexes formed on the non-template DNA...
Subtle-seq reveals frequent ageing-associated chromosome fragmentation on nucleosome core DNA
Telomere healing seals the broken ends of DNA double-strand breaks by adding de novo telomeres. In the ciliate Paramecium, telomere healing results in chromosome fragmentation, which ultimately leads to clonal ageing. Despite its importance, where and how chromosomes fragment and undergo telomere healing, and to what extent sequence preferences exist, remain poorly understood. To investigate chromosome fragmentation, we enriched for telomere-containing sequences from the complex, highly...