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Type: Journal article
Title: Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis
Author: Łuksza, M.
Kanaan, J.
Marthiens, V.
Lane, S.
Jones, K.
Terret, M.
Basto, R.
Verlhac, M.
Citation: The Journal of Cell Biology, 2018; 217(10):3416-3430
Publisher: Rockefeller University Press
Issue Date: 2018
ISSN: 0021-9525
Statement of
Marion Manil-Ségalen, Małgorzata Łuksza, Joanne Kanaan, Véronique Marthiens, Simon I.R. Lane, Keith T. Jones, Marie-Emilie Terret, Renata Basto, Marie-Hélène Verlhac
Abstract: Mouse female meiotic spindles assemble from acentriolar microtubule-organizing centers (aMTOCs) that fragment into discrete foci. These are further sorted and clustered to form spindle poles, thus providing balanced forces for faithful chromosome segregation. To assess the impact of aMTOC biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master microtubule-organizing center regulator. Excessive microtubule nucleation from these fragmented aMTOCs accelerated spindle assembly dynamics. Prematurely formed spindles promoted the breakage of three different fragilized bivalents, generated by the presence of recombined Lox P sites. Reducing the density of microtubules significantly diminished the extent of chromosome breakage. Thus, improper spindle forces can lead to widely described yet unexplained chromosomal structural anomalies with disruptive consequences on the ability of the gamete to transmit an uncorrupted genome.
Keywords: Oocytes; Chromosomes, Mammalian; Microtubule-Organizing Center; Animals; Mice, Transgenic; Mice; Meiosis; Female; Spindle Apparatus; Gene Editing
Rights: © 2018 Manil-Ségalen et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https:// creativecommons .org/ licenses/ by/ 4 .0/ ).
RMID: 0030099117
DOI: 10.1083/jcb.201806072
Appears in Collections:Genetics publications

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