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Catastrophic endgames: emerging mechanisms of telomere-driven genomic instability

Cleal, Kez and Baird, Duncan ORCID: 2020. Catastrophic endgames: emerging mechanisms of telomere-driven genomic instability. Trends in Genetics 36 (5) , pp. 347-359. 10.1016/j.tig.2020.02.001

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When cells progress to malignancy, they must overcome a final telomere-mediated proliferative lifespan barrier called replicative crisis. Crisis is characterized by extensive telomere fusion that drives widespread genomic instability, mitotic arrest, hyperactivation of autophagy, and cell death. Recently, it has become apparent that that the resolution of dicentric chromosomes, which arise from telomere fusions during crisis, can initiate a sequence of events that leads to chromothripsis, a form of extreme genomic catastrophe. Chromothripsis is characterized by localized genomic regions containing tens to thousands of rearrangements and it is becoming increasingly apparent that chromothripsis occurs widely across tumor types and has a clinical impact. Here we discuss how telomere dysfunction can initiate genomic complexity and the emerging mechanisms of chromothripsis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0168-9525
Date of First Compliant Deposit: 19 March 2020
Date of Acceptance: 13 February 2020
Last Modified: 27 Jan 2023 07:18

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