Chromosomal Rearrangements and Chromothripsis: The Alternative End Generation Model

Author:

de Groot Daniel,Spanjaard Aldo,Hogenbirk Marc A.,Jacobs HeinzORCID

Abstract

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.

Funder

Dutch Cancer Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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