Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 3, Pages 626-631Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1517628112
Keywords
chromosome segregation; micronuclei; mitosis; preimplantation development; embryo mosaicism
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Funding
- Fondation Jean-Louis Levesque
- Natural Sciences and Engineering Research Council of Canada
- Canadian Foundation for Innovation
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology-Japan
- Reseau Quebecois en Reproduction
- Lalor Foundation
- Grants-in-Aid for Scientific Research [25116005] Funding Source: KAKEN
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Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.
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