Cleal, Kez, Jones, Rhiannon E., Grimstead, Julia W., Hendrickson, Eric A. and Baird, Duncan M.  ORCID: https://orcid.org/0000-0001-8408-5467
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: | Schools > Medicine Professional Services > 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: | 22 Sep 2024 15:39 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/121094 |
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