Induction of chromosome-specific micronuclei and chromothripsis by centromere inactivation

Yu Fen Lin, Qing Hu, Alison Guyer, Daniele Fachinetti, Peter Ly

Research output: Chapter in Book/Report/Conference proceedingChapter


Chromothripsis describes the catastrophic fragmentation of individual chromosomes followed by its haphazard reassembly into a derivative chromosome harboring complex rearrangements. This process can be initiated by mitotic cell division errors when one or more chromosomes aberrantly mis-segregate into micronuclei and acquire extensive DNA damage. Approaches to induce the formation of micronuclei encapsulating random chromosomes have been used; however, the eventual reincorporation of the micronucleated chromosome into daughter cell nuclei poses a challenge in tracking the chromosome for multiple cell cycles. Here we outline an approach to genetically engineer stable human cell lines capable of efficient chromosome-specific micronuclei induction. This strategy, which targets the CENP-B-deficient Y chromosome centromere for inactivation, allows the stepwise process of chromothripsis to be experimentally recapitulated, including the mechanisms and timing of chromosome fragmentation. Lastly, we describe the integration of a selection marker onto the micronucleated Y chromosome that enables the diverse genomic rearrangement landscape arising from micronuclei formation to be interrogated.

Original languageEnglish (US)
Title of host publicationMethods in Cell Biology
PublisherAcademic Press Inc.
StateAccepted/In press - 2022

Publication series

NameMethods in Cell Biology
ISSN (Print)0091-679X


  • Centromere
  • Chromosome segregation
  • Chromothripsis
  • Micronuclei

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Induction of chromosome-specific micronuclei and chromothripsis by centromere inactivation'. Together they form a unique fingerprint.

Cite this