Premature chromatin condensation upon accumulation of NIMA.
The NIMA protein kinase of Aspergillus nidulans is required for the G2/M transition of the cell cycle. Mutants lacking NIMA arrest without morphological characteristics of mitosis, but they do contain an activated p37nimX kinase (the Aspergillus homologue of p34cdc2). To gain a better understanding of NIMA function we have investigated the effects of expressing various NIMA constructs in Aspergillus, fission yeast and human cells. Our experiments have shown that the instability of the NIMA protein requires sequences in the non-catalytic C-terminus of the protein. Removal of this domain results in a stable protein that, once accumulated, promotes a lethal premature condensation of chromatin without any other aspects of mitosis. Similar effects were also observed in fission yeast and human cells accumulating Aspergillus NIMA. This phenotype is independent of cell cycle progression and does not require p34cdc2 kinase activity. As gain of NIMA function by accumulation results in premature chromatin condensation, and loss of NIMA function results in an inability to enter mitosis, we propose that NIMA functions in G2 to promote the condensation of chromatin normally associated with entry into mitosis.
Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK.
M J
MJ
O'Connell
C
C
Norbury
P
P
Nurse
D017209:Apoptosis / Q000235:genetics; D001233:Aspergillus nidulans / Q000166:cytology / Q000201:enzymology; D001483:Base Sequence; D002384:Catalysis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics
D018797:Cell Cycle Proteins; D002843:Chromatin; D011994:Recombinant Proteins; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; D017346:Protein Serine-Threonine Kinases; C000606921:fin1 protein, S pombe