TY  - JOUR
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
Y1  - 2019/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 737 
EP  - 749 
DO  - 10.1101/gr.240705.118 
VL  - 29 
IS  - 5 
UR  - http://genome.cshlp.org/content/29/5/737.abstract 
N2  - 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. 
ER  -