MCPH1, mutated in primary microcephaly, is required for efficient chromosome alignment during mitosis

M. Arroyo, R. Kuriyama, M. Trimborn, D. Keifenheim, A. Cañuelo, A. Sánchez, D. J. Clarke, J. A. Marchal

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

MCPH1 gene, mutated in primary microcephaly, regulates cell progression into mitosis. While this role has been extensively investigated in the context of DNA damage, its function during unperturbed cell cycles has been given less attention. Here we have analyzed the dynamics of chromosome condensation and cell cycle progression in MCPH1 deficient cells under undamaging conditions. Our study demonstrates that chromosome condensation is uncoupled from cell cycle progression when MCPH1 function is lacking, resulting in cells that prematurely condense their chromosomes during mid G2-phase and delay decondensation at the completion of mitosis. However, mitosis onset occurs on schedule in MCPH1 deficient cells. We also revealed active Cdk1 to be mandatory for the premature onset of chromosome condensation during G2 and the maintenance of the condensed state thereafter. Interestingly, a novel cellular phenotype was observed while monitoring cell cycle progression in cells lacking MCPH1 function. Specifically, completion of chromosome alignment at the metaphase plate was significantly delayed. This deficiency reveals that MCPH1 is required for efficient chromosome biorientation during mitosis.

Original languageEnglish (US)
Article number13019
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Bibliographical note

Funding Information:
This work was supported by Junta de Andalucía (Funding program ‘Ayudas a grupos de investigación’, reference BIO 220). M. Arroyo PhD is granted by University of Jaén (Spain), and was provided with travelling grants EMBO and “Escuela de Doctorado” (University of Jaén, Spain). The authors express their gratitude to H. Neitzel (Berlin, Germany) for providing the lymphoblast cell lines used in this study; C. Fisher and G. Marques (University of Minnesota, US) for technical assistance; and T. Hirano (RIKEN, Japan) for providing the antibody against MCPH1. Research at laboratory of R. Kuriyama was financially supported by NSF (MCB1140033). Technical and human support provided by CICT of Universidad de Jaén (UJA, MINECO, Junta de Andalucía, FEDER) is gratefully acknowledged.

Publisher Copyright:
© 2017 The Author(s).

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