Oncotarget

Research Papers: Chromosome:

CDK1 and PLK1 coordinate the disassembly and reassembly of the nuclear envelope in vertebrate mitosis

Ines J de Castro, Raquel Sales Gil, Lorena Ligammari, Maria Laura Di Giacinto and Paola Vagnarelli _

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Oncotarget. 2018; 9:7763-7773. https://doi.org/10.18632/oncotarget.23666

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Abstract

Ines J de Castro1,2,*, Raquel Sales Gil1,*, Lorena Ligammari1, Maria Laura Di Giacinto1 and Paola Vagnarelli1

1College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, UB8 3PH, UK

2Current address: Department of Infectious Diseases, Integrative Virology, University Hospital Heidelberg and German Center for Infection Research (DZIF), 69120 Heidelberg, Germany

*These authors contributed equally to this work

Correspondence to:

Paola Vagnarelli, email: Paola.Vagnarelli@Brunel.ac.uk

Keywords: nuclear envelope; polo Like Kinase (PLK1); nuclear pore complex (NPC); lamin A; micronuclei; chromosome

Received: August 30, 2017     Accepted: October 31, 2017     Published: December 23, 2017

ABSTRACT

Micronuclei (MN) arise from chromosomes or fragments that fail to be incorporated into the primary nucleus after cell division. These structures are a major source of genetic instability caused by DNA repair and replication defects coupled to aberrant Nuclear Envelope (NE). These problems ultimately lead to a spectrum of chromosome rearrangements called chromothripsis, a phenomenon that is a hallmark of several cancers. Despite its importance, the molecular mechanism at the origin of this instability is still not understood. Here we show that lagging chromatin, although it can efficiently assemble Lamin A/C, always fails to recruit Nuclear Pore Complexes (NPCs) proteins and that Polo-Like Kinase (PLK1) negatively regulates NPC assembly. We also provide evidence for the requirement of PLK1 activity for the disassembly of NPCs, but not Lamina A/C, at mitotic entry. Altogether this study reveals the existence of independent regulatory pathways for Lamin A/C and NPC reorganization during mitosis where Lamin A/C targeting to the chromatin is controlled by CDK1 activity (a clock-based model) while the NPC loading is also spatially monitored by PLK1.


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