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Title

Chromothripsis: Breakage-fusion-bridge over and over again

AuthorsSánchez Sorzano, Carlos Óscar; Pascual-Montano, Alberto; Sánchez de Diego, Ainhoa; Martínez-A, Carlos; Van Wely, Karel H. M.
Keywordschromothripsis
breakage-fusion-bridge
chromosomal instability
centromere fission
mitosis
telomere
Issue Date1-Jul-2013
PublisherLandes Bioscience
CitationCell Cycle 12(13): 2016-2023 (2013)
Series12
13
AbstractThe acquisition of massive but localized chromosome translocations, a phenomenon termed chromothripsis, has received widespread attention since its discovery over a year ago. Until recently, chromothripsis was believed to originate from a single catastrophic event, but the molecular mechanisms leading to this event are yet to be uncovered. Because a thorough interpretation of the data is missing, the phenomenon itself has wrongly acquired the status of a mechanism used to justify many kinds of complex rearrangements. Although the assumption that all translocations in chromothripsis originate from a single event has met with criticism, satisfactory explanations for the intense but localized nature of this phenomenon are still missing. Here, we show why the data used to describe massive catastrophic rearrangements are incompatible with a model comprising a single event only, and propose a molecular mechanism in which a combination of known cellular pathways accounts for chromothripsis. Instead of a single traumatic event, the protection of undamaged chromosomes by telomeres can limit repetitive breakage-fusion-bridge events to a single chromosome arm. Ultimately, common properties of chromosomal instability, such as aneuploidy and centromere fission, might establish the complex genetic pattern observed in this genomic state.
Publisher version (URL)http://dx.doi.org/10.4161/cc.25266
URIhttp://hdl.handle.net/10261/78972
DOI10.4161/cc.25266
ISSN1538-4101
E-ISSN1551-4005
Appears in Collections:(CNB) Artículos
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