NuMA is an abundant long coiled-coil protein that plays a prominent role in spindle organization during mitosis. In interphase, NuMA is localized to the nucleus and hypothesized to control gene expression and chromatin organization. However, because of the prominent mitotic phenotype upon NuMA loss, its precise function in the interphase nucleus remains elusive. Here, we report that NuMA is associated with chromatin in interphase and prophase but released upon nuclear envelope breakdown (NEBD) by the action of Cdk1. We uncover that NuMA directly interacts with DNA via evolutionarily conserved sequences in its C-terminus. Notably, the expression of the DNA-binding deficient mutant of NuMA affects chromatin decondensation at the mitotic exit, and nuclear shape in interphase. We show that the nuclear shape defects observed upon mutant NuMA expression are due to its potential to polymerize into higher-order fibrillar structures. Overall, this work establishes the spindle independent function of NuMA in choreographing proper chromatin decompaction and nuclear shape by directly associating with the DNA.

NuMA是一种丰富的长卷曲螺旋蛋白，在有丝分裂期间在纺锤体组织中起着重要作用。在相间期，NuMA定位于细胞核，并假设其可控制基因表达和染色质组织。但是，由于在NuMA缺失时突出的有丝分裂表型，其在相间核中的精确功能仍然难以捉摸。在这里，我们报告NuMA与相间和前期的染色质相关联，但通过Cdk1的作用在核被膜破裂（NEBD）时释放。我们发现NuMA通过其C末端的进化保守序列直接与DNA相互作用。值得注意的是，NuMA的DNA结合缺陷型突变体的表达会影响有丝分裂出口处的染色质去缩合和相间核形状。我们表明突变NuMA表达上观察到的核形状缺陷是由于其聚合成更高阶纤维状结构的潜力。总的来说，这项工作通过直接与DNA结合，在编排适当的染色质脱质和核形状方面建立了NuMA的纺锤体独立功能。