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 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.

Automated summary

Chromothripsis is a genetic phenomenon characterized by numerous clustered chromosomal rearrangements occurring in a single catastrophic event, often associated with cancer and congenital diseases. The prevailing models suggest that prior to chromothripsis, a large number of DNA double-strand breaks (DSBs) must exist, indicating chromosomal shattering before rearrangements occur. However, our proposal of chromothripsis as the result of successive chromatin rearrangements, called Alternative End Generation (AEG), is based on the preference of a DNA end to rearrange in a proximal accessible region. Accordingly, chromothripsis is the end product of this domino-like reaction in a single catastrophic event.