The mode of mitosis is dramatically modified by deletion of a single nuclear pore complex gene in Aspergillus nidulans

被引:4
作者
Chemudupati, Mahesh [1 ,2 ,3 ]
Johns, Matthew [1 ]
Osmani, Stephen A. [1 ,2 ]
机构
[1] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA
[2] Ohio State Univ, Ohio State Biochem Program, Columbus, OH 93210 USA
[3] Ohio State Univ, Wexner Med Ctr, Dept Microbial Infect & Immun, Columbus, OH 43210 USA
基金
美国国家卫生研究院;
关键词
Mitosis; Nuclear envelope; Nucleolus; Chromatin; Nucleoporin; rDNA; CELL-CYCLE; ENVELOPE; CHECKPOINT; NUCLEOPORINS; ORGANIZATION; CHROMOSOMES; SEPARATION; MOVEMENT; DYNAMICS; CANCER;
D O I
10.1016/j.fgb.2019.04.010
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Nuclear pore complex (NPC) proteins (Nups) play multiple roles during mitosis. In this study we expand these roles and reveal that in Aspergillus nidulans, compromising the core Nup84-120 subcomplex of the NPC modifies the mitotic behavior of the nuclear envelope (NE). In wildtype cells, the NE undergoes simultaneous double pinching events to separate daughter nuclei during mitotic exit, whereas in Nup84-120 complex mutants, only one restriction of the NE is observed. Investigating the basis for this modified behavior of the NE in Nup deleted cells uncovered previously unrealized roles for core Nups in mitotic exit. During wildtype anaphase, the NE surrounds the two separating daughter DNA masses which typically flank the central nucleolus, to form three distinct nuclear compartments. In contrast, deletion of core Nups frequently results in early nucleolar eviction from the mitotic nucleus, in turn causing an uncharacteristic dumbbell-shaped NE morphology of anaphase nuclei with a nuclear membrane bridge connecting the two forming G1 nuclei. Importantly, the absence of the nucleolus between the separating daughter nuclei during anaphase delays chromosome segregation and progression into G1 as nuclei remain connected by chromatin bridges. Proteins localizing to late segregating chromosome arms are observed between forming daughter nuclei, and the mitotic spindle fails to resolve in a timely manner. These chromatin bridges are occupied by the Aurora kinase until nuclei have fully separated, suggesting involvement of Aurora in monitoring mitotic spindle and nuclear membrane resolution during mitotic exit. Our findings thus reveal a novel requirement for core Nups in mediating nucleolar positioning during mitosis, which dictates the pattern of NE fissions during karyokinesis and facilitates normal chromosome segregation. The findings additionally demonstrate that the mode of mitosis can be dramatically modified by deletion of a single NPC gene and reveals surprising fluidity in mitotic mechanisms.
引用
收藏
页码:72 / 81
页数:10
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