From Telomere Crisis via Dicentric Chromosomes to Kataegis and Chromothripsis

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Chromothripsis and Kataegis Induced by Telomere Crisis

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 br...

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Telomere dysfunction and chromothripsis.

Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic e...

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Telomere Crisis and Chromosome Shattering in Cancer

Although cancer development involves gradual step-wise mutational alterations, recent work has pointed to an additional contribution of episodic massive chromosome shattering phenomena, including chromoplexy and chromothripsis. How chromoplexy and chromothripsis are initiated is unknown. We hypothesize that chromosome shattering originates from end-to-end fused dicentric chromosomes, which occu...

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Telomere Disruption Results in Non-Random Formation of De Novo Dicentric Chromosomes Involving Acrocentric Human Chromosomes

Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since ther...

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Dicentric breakage at telomere fusions.

Nonhomologous end-joining (NHEJ) inhibition at telomeres ensures that native chromosome ends do not fuse together. But the occurrence and consequences of rare telomere fusions are not well understood. It is notably unclear whether a telomere fusion could be processed to restore telomere ends. Here we address the behavior of individual dicentrics formed by telomere fusion in the yeast Saccharomy...

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ژورنال

عنوان ژورنال: Molecular Syndromology

سال: 2015

ISSN: 1661-8769,1661-8777

DOI: 10.1159/000443805