Chromothripsis and Kataegis Induced by Telomere Crisis.

ABSTRACT: Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 μm chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showe

SUBMITTER: Maciejowski J 

PROVIDER: S-EPMC4687025 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature