Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response.

ABSTRACT: Identifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. Eroded telomeres also fused with genomic loci actively engaged in transcription, with particular enrichment in long genes. Both gross copy number alterations and transcriptional response

SUBMITTER: Liddiard K 

PROVIDER: S-EPMC7787266 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature