title: The NIMA kinase is required to execute stage-specific mitotic functions after initiation of mitosis.
abstract: The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events.
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Govindaraghavan
authors.forename: Alisha A
authors.initials: AA
authors.lastname: Lad
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Osmani
mesh_terms: D001233:Aspergillus nidulans / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics*; D000072380:NIMA-Related Kinase 1; D022022:Nuclear Pore / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D005656:Fungal Proteins; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases