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Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis

Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis
Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis
Mouse female meiotic spindles assemble from acentriolar MTOCs (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 aMTOCs biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master MTOC 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 diminished significantly 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.
1540-8140
Manil-Ségalen, Marion
30d40388-d091-4db4-b757-0c1d19abf129
Łuksza, Małgorzata
ea6ab706-f76b-4436-8eaf-43a0b7520aac
Kannaan, Joanne
3adb4126-9b10-4e8e-b562-2ce4579fb1c9
Marthiens, Véronique
93cab6fe-646f-474a-b45c-d3c67c823c9d
Lane, Simon
8e80111f-5012-4950-a228-dfb8fb9df52d
Jones, Keith
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Terret, Marie-Emilie
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Basto, Renata
f52d4902-3f10-4030-a790-1e2c44dce98a
Verlhac, Marie-Hélène
62ba628c-3cca-41da-8121-729eb519ae7a
Manil-Ségalen, Marion
30d40388-d091-4db4-b757-0c1d19abf129
Łuksza, Małgorzata
ea6ab706-f76b-4436-8eaf-43a0b7520aac
Kannaan, Joanne
3adb4126-9b10-4e8e-b562-2ce4579fb1c9
Marthiens, Véronique
93cab6fe-646f-474a-b45c-d3c67c823c9d
Lane, Simon
8e80111f-5012-4950-a228-dfb8fb9df52d
Jones, Keith
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Terret, Marie-Emilie
8a0253b8-b230-4526-bd43-1f2abe1769cc
Basto, Renata
f52d4902-3f10-4030-a790-1e2c44dce98a
Verlhac, Marie-Hélène
62ba628c-3cca-41da-8121-729eb519ae7a

Manil-Ségalen, Marion, Łuksza, Małgorzata, Kannaan, Joanne, Marthiens, Véronique, Lane, Simon, Jones, Keith, Terret, Marie-Emilie, Basto, Renata and Verlhac, Marie-Hélène (2018) Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis. The Journal of Cell Biology, 217 (6). (doi:10.1083/jcb.201806072).

Record type: Article

Abstract

Mouse female meiotic spindles assemble from acentriolar MTOCs (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 aMTOCs biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master MTOC 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 diminished significantly 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.

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More information

Accepted/In Press date: 20 July 2018
e-pub ahead of print date: 6 August 2018

Identifiers

Local EPrints ID: 422791
URI: http://eprints.soton.ac.uk/id/eprint/422791
ISSN: 1540-8140
PURE UUID: a784072c-7644-44e6-909b-3603e48cfdd3
ORCID for Simon Lane: ORCID iD orcid.org/0000-0002-8155-0981
ORCID for Keith Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 06 Aug 2018 16:30
Last modified: 22 Nov 2021 03:04

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Contributors

Author: Marion Manil-Ségalen
Author: Małgorzata Łuksza
Author: Joanne Kannaan
Author: Véronique Marthiens
Author: Simon Lane ORCID iD
Author: Keith Jones ORCID iD
Author: Marie-Emilie Terret
Author: Renata Basto
Author: Marie-Hélène Verlhac

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