RT Journal Article
SR Electronic
T1 CDK1 and PLK1 co-ordinate the disassembly and re-assembly of the Nuclear Envelope in vertebrate mitosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 185660
DO 10.1101/185660
A1 Ines J de Castro
A1 Raquel Sales Gil
A1 Lorena Ligammari
A1 Maria Laura Di Giacinto
A1 Paola Vagnarelli
YR 2017
UL http://biorxiv.org/content/early/2017/09/07/185660.abstract
AB 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 the 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 targeting to the chromatin is controlled by CDK1 activity (a clock-based model) while the NPC loading is also spatially monitored by PLK1.