Chromothripsis from DNA damage in micronuclei View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-06

AUTHORS

Cheng-Zhong Zhang, Alexander Spektor, Hauke Cornils, Joshua M. Francis, Emily K. Jackson, Shiwei Liu, Matthew Meyerson, David Pellman

ABSTRACT

Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed that it could occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here, using a combination of live cell imaging and single-cell genome sequencing, we demonstrate that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis. These events are restricted to the mis-segregated chromosome and occur within one cell division. We demonstrate that the mechanism for chromothripsis can involve the fragmentation and subsequent reassembly of a single chromatid from a micronucleus. Collectively, these experiments establish a new mutational process of which chromothripsis is one extreme outcome. More... »

PAGES

179

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature14493

DOI

http://dx.doi.org/10.1038/nature14493

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001545095

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26017310


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