ABSTRACT
Chromatin structure and dynamics are highly controlled and regulated processes that play an essential role in many aspects of cell biology. The chromatin transition stages and the factors that control this process are regulated by post-translation modifications, including phosphorylation. While the role of protein kinases in chromatin dynamics has been quite well studied, the nature and regulation of the counteracting phosphatases represent an emerging field but are still at their infancy. In this review we summarize the current literature on phosphatases involved in the regulation of chromatin structure and dynamics, with emphases on the major knowledge gaps that should require attention and more investigation.
Subject(s)
Chromatin Assembly and Disassembly/physiology , Phosphoprotein Phosphatases/metabolism , Phosphoprotein Phosphatases/physiology , Animals , Chromatin/genetics , Chromatin/metabolism , Chromatin/physiology , Chromatin Assembly and Disassembly/genetics , DNA/genetics , DNA Methylation/physiology , DNA Repair/physiology , DNA Replication/physiology , Epigenesis, Genetic/physiology , Gene Expression Regulation/physiology , Histones/genetics , Histones/metabolism , Humans , Nucleosomes/metabolism , Phosphorylation , Protein Processing, Post-Translational/physiology , Telomere/metabolismABSTRACT
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.