Chromosomal Rearrangements and Chromothripsis: The Alternative End Generation Model

Chromothripsis defines a genetic phenomenon where up to hundreds of clustered chromosomal rearrangements can arise in a single catastrophic event. The phenomenon is associated with cancer and congenital diseases. Most current models on the origin of chromothripsis suggest that prior to chromatin res...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-01, Vol.24 (1), p.794
Main Authors: de Groot, Daniel, Spanjaard, Aldo, Hogenbirk, Marc A, Jacobs, Heinz
Format: Article
Language:English
Subjects:
Chromatin
Chromosome Aberrations
Chromothripsis
DNA - genetics
DNA Breaks, Double-Stranded
Humans
Review
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Summary:Chromothripsis defines a genetic phenomenon where up to hundreds of clustered chromosomal rearrangements can arise in a single catastrophic event. The phenomenon is associated with cancer and congenital diseases. Most current models on the origin of chromothripsis suggest that prior to chromatin reshuffling numerous DNA double-strand breaks (DSBs) have to exist, i.e., chromosomal shattering precedes rearrangements. However, the preference of a DNA end to rearrange in a proximal accessible region led us to propose chromothripsis as the reaction product of successive chromatin rearrangements. We previously coined this process Alternative End Generation (AEG), where a single DSB with a repair-blocking end initiates a domino effect of rearrangements. Accordingly, chromothripsis is the end product of this domino reaction taking place in a single catastrophic event.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms24010794