CDK1 and PLK1 coordinate the disassembly and reassembly of the nuclear envelope in vertebrate mitosis.
CDK1 and PLK1 coordinate the disassembly and reassembly of the nuclear envelope in vertebrate mitosis.
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DOI：
10.18632/oncotarget.23666
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发表时间：
2018-01-30
期刊：
影响因子：
--
通讯作者：
Vagnarelli P
中科院分区：
文献类型：
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作者：
de Castro IJ;Gil RS;Ligammari L;Di Giacinto ML;Vagnarelli P
微核（MN）产生于细胞分裂后染色体或片段未能并入初代细胞核。这些结构是由DNA修复和复制缺陷与异常核膜（NE）耦合引起的遗传不稳定的主要来源。这些问题最终会导致一系列染色体重排，称为染色体断裂，这种现象是几种癌症的标志。尽管它很重要，但这种不稳定性起源的分子机制仍然不清楚。本研究表明，虽然滞后染色质可以有效地组装Lamin A/C，但它总是不能招募核孔复合物（NPCs）蛋白，并且polo样激酶（PLK1）负调控NPCs的组装。我们还提供了证据，证明在有丝分裂进入时，NPCs的拆卸需要PLK1活性，而不是层A/C。总之，本研究揭示了有丝分裂期间Lamin A/C和NPC重组的独立调控途径的存在，其中Lamin A/C靶向染色质受CDK1活性（基于时钟的模型）控制，而NPC装载也受PLK1的空间监测。
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.