%0 Journal Article
%T Chromothripsis during telomere crisis is independent of NHEJ, and consistent with a replicative origin
%A Duncan M. Baird
%A Eric A. Hendrickson
%A Julia W. Grimstead
%A Kez Cleal
%A Rhiannon E. Jones
%J Genome Research
%D 2019
%R http://www.genome.org/cgi/doi/10.1101/gr.240705.118
%X 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
%U https://genome.cshlp.org/content/29/5/737.abstract