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

نویسندگان

چکیده

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 transcriptome developments characterize the transition dynamic proliferation into replicative crisis. Progression through was associated with abundant intra-chromosomal telomere fusions increasing asymmetry reduced microhomology usage, suggesting shifts DNA repair capacity. Eroded telomeres also fused loci actively engaged transcription, particular enrichment long genes. Both gross copy number alterations transcriptional responses likely underpin elevated frequencies fusion chromosomes 9, 16, 17, 19 most exceptionally, chromosome 12. Juxtaposition crisis-regulated genes undergoing de novo recombination exposes collusive contributions cellular stress evolving cancer genome.

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ژورنال

عنوان ژورنال: NAR cancer

سال: 2021

ISSN: ['2632-8674']

DOI: https://doi.org/10.1093/narcan/zcaa044