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

Kez Cleal, Rhiannon E. Jones, Julia W. Grimstead, Eric A Hendrickson, Duncan M. Baird

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 nonhomologous 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 a telomere crisis arise via a replicative repair process involving template switching.

Original languageEnglish (US)
Pages (from-to)737-749
Number of pages13
JournalGenome Research
Volume29
Issue number5
DOIs
StatePublished - May 1 2019

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Telomere
Genome
Genomic Instability
Sequence Analysis
Chromothripsis
Population

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

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; Baird, Duncan M.

In: Genome Research, Vol. 29, No. 5, 01.05.2019, p. 737-749.

Research output: Contribution to journalArticle

Cleal, Kez ; Jones, Rhiannon E. ; Grimstead, Julia W. ; Hendrickson, Eric A ; Baird, Duncan M. / Chromothripsis during telomere crisis is independent of NHEJ, and consistent with a replicative origin. In: Genome Research. 2019 ; Vol. 29, No. 5. pp. 737-749.
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