RT Journal
A1 Cleal, Kez
A1 Jones, Rhiannon E.
A1 Grimstead, Julia W.
A1 Hendrickson, Eric A.
A1 Baird, Duncan M.
T1 Chromothripsis during telomere crisis is independent of NHEJ, and consistent with a replicative origin
JF Genome Research 
JO Genome Research 
YR 2019 
FD May 01 
VO 29 
IS 5 
SP 737 
OP 749 
DO 10.1101/gr.240705.118 
UL http://genome.cshlp.org/content/29/5/737.abstract 
AB 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.