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Chromothripsis during telomere crisis is independent of NHEJ and consistent with a replicative origin

Cleal, Kez, Jones, Rhiannon E., Grimstead, Julia W., Hendrickson, Eric A. and Baird, Duncan M. 2019. Chromothripsis during telomere crisis is independent of NHEJ and consistent with a replicative origin. Genome Research 29 (5) , pp. 737-749. 10.1101/gr.240705.118

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Abstract

Telomere erosion, dysfunction and fusion can lead to a state of cellular crisis characterized by large-scale genome instability. We investigated the impact of a telomere-driven crisis on the structural integrity of the genome by undertaking whole genome sequence analyses of clonal populations of cells that had escaped crisis. Quantification of large-scale structural variants revealed patterns of rearrangement consistent with chromothripsis, but formed in the absence of functional non-homologous end joining pathways. Rearrangements frequently consisted of short fragments with complex mutational patterns, with a repair topology that deviated from randomness showing preferential repair to local regions or exchange between specific loci. We find evidence of telomere involvement with an enrichment of fold-back inversions demarcating clusters of rearrangements. Our data suggest that chromothriptic rearrangements caused by telomere crisis arise via a replicative repair process involving template switching.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Cold Spring Harbor Laboratory Press
ISSN: 1088-9051
Date of First Compliant Deposit: 25 March 2019
Date of Acceptance: 11 March 2019
Last Modified: 05 Jun 2019 13:46
URI: http://orca.cf.ac.uk/id/eprint/121094

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