Cleal, Kez, Jones, Rhiannon E., Grimstead, Julia W., Hendrickson, Eric A. and Baird, Duncan M. ![]() ![]() |
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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 |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Advanced Research Computing @ Cardiff (ARCCA) |
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 May 2023 15:35 |
URI: | https://orca.cardiff.ac.uk/id/eprint/121094 |
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