Xu Yu-Xin, Manley James L
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Cell Cycle. 2007 Dec 1;6(23):2896-901. doi: 10.4161/cc.6.23.4977. Epub 2007 Aug 29.
Topoisomerase (Topo) IIalpha and condensin are essential for formation of mitotic chromosomes. However, the mechanism by which these two major components assemble during the chromosome condensation process had been unclear. Recent studies have revealed a coordinated and cooperative process, by which TopoIIalpha functions early to form an axis scaffold, whereas condensin complexes assemble at a later stage critical for chromosome integrity and subsequent segregation. Extending these observations, we recently found that the phosphorylation-dependent prolyl isomerase Pin1 is directly linked to the process. This conclusion is based on the observation of strong and extensive interactions of Pin1 with chromatin specifically at G2/M phase. Pin1 modulates the mitotic phosphorylation of TopoIIalpha by cdc2/cyclinB and promotes the association of phosphorylated TopoIIalpha with DNA elements to form an axis scaffold complex. The evidence highlights a critical role of Pin1 via its regulation of mitotic phosphorylation of key components in the chromosome condensation process.
拓扑异构酶（Topo）IIα和凝聚素对于有丝分裂染色体的形成至关重要。然而，这两个主要成分在染色体凝聚过程中组装的机制尚不清楚。最近的研究揭示了一个协调且协同的过程，即TopoIIα早期发挥作用形成轴支架，而凝聚素复合物在对染色体完整性和后续分离至关重要的后期阶段组装。扩展这些观察结果，我们最近发现磷酸化依赖性脯氨酰异构酶Pin1与该过程直接相关。这一结论基于观察到Pin1与染色质在G2/M期有强烈且广泛的相互作用。Pin1通过cdc2/细胞周期蛋白B调节TopoIIα的有丝分裂磷酸化，并促进磷酸化的TopoIIα与DNA元件结合形成轴支架复合物。证据突出了Pin1通过调节染色体凝聚过程中关键成分的有丝分裂磷酸化所起的关键作用。
