Abstract
Mutation of nimA reversibly arrests cells in late G2 and nimA overexpression promotes premature mitosis. Here we demonstrate that the product of nimA (designated NIMA) has protein kinase activity that can phosphorylate beta-casein but not histone proteins. NIMA kinase activity is cell cycle regulated being 20-fold higher at mitosis when compared to S-phase arrested cells. NIMA activation is normally required in G2 to initiate chromosome condensation, to nucleate spindle pole body microtubules, and to allow an MPM-2 specific mitotic phosphorylation. All three of these mitotic events can occur in the absence of activated NIMA when the bimE gene is mutated (bimE7). However, the bimE7 mutation cannot completely bypass the requirement for nimA during mitosis as entry into mitosis in the absence of NIMA activation results in major mitotic defects that affect both the organization of the nuclear envelope and mitotic spindle. Thus, although nimA plays an essential but limited role during mitosis, mutation of nimA arrests all of mitosis. We therefore propose that mutation of nimA prevents mitotic initiation due to a checkpoint arrest that is negatively mediated by bimE. The checkpoint ensures that mitosis is not initiated until NIMA is mitotically activated.
Full text
PDF










Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arion D., Meijer L., Brizuela L., Beach D. cdc2 is a component of the M phase-specific histone H1 kinase: evidence for identity with MPF. Cell. 1988 Oct 21;55(2):371–378. doi: 10.1016/0092-8674(88)90060-8. [DOI] [PubMed] [Google Scholar]
- Bergen L. G., Morris N. R. Kinetics of the nuclear division cycle of Aspergillus nidulans. J Bacteriol. 1983 Oct;156(1):155–160. doi: 10.1128/jb.156.1.155-160.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bergen L. G., Upshall A., Morris N. R. S-phase, G2, and nuclear division mutants of Aspergillus nidulans. J Bacteriol. 1984 Jul;159(1):114–119. doi: 10.1128/jb.159.1.114-119.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Booher R. N., Alfa C. E., Hyams J. S., Beach D. H. The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization. Cell. 1989 Aug 11;58(3):485–497. doi: 10.1016/0092-8674(89)90429-7. [DOI] [PubMed] [Google Scholar]
- Brizuela L., Draetta G., Beach D. Activation of human CDC2 protein as a histone H1 kinase is associated with complex formation with the p62 subunit. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4362–4366. doi: 10.1073/pnas.86.12.4362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis F. M., Tsao T. Y., Fowler S. K., Rao P. N. Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci U S A. 1983 May;80(10):2926–2930. doi: 10.1073/pnas.80.10.2926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doonan J. H., Morris N. R. The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1. Cell. 1989 Jun 16;57(6):987–996. doi: 10.1016/0092-8674(89)90337-1. [DOI] [PubMed] [Google Scholar]
- Draetta G., Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. doi: 10.1016/0092-8674(88)90175-4. [DOI] [PubMed] [Google Scholar]
- Edelman A. M., Blumenthal D. K., Krebs E. G. Protein serine/threonine kinases. Annu Rev Biochem. 1987;56:567–613. doi: 10.1146/annurev.bi.56.070187.003031. [DOI] [PubMed] [Google Scholar]
- Engle D. B., Doonan J. H., Morris N. R. Cell-cycle modulation of MPM-2-specific spindle pole body phosphorylation in Aspergillus nidulans. Cell Motil Cytoskeleton. 1988;10(3):434–437. doi: 10.1002/cm.970100310. [DOI] [PubMed] [Google Scholar]
- Engle D. B., Osmani S. A., Osmani A. H., Rosborough S., Xin X. N., Morris N. R. A negative regulator of mitosis in Aspergillus is a putative membrane-spanning protein. J Biol Chem. 1990 Sep 25;265(27):16132–16137. [PubMed] [Google Scholar]
- Enoch T., Nurse P. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell. 1990 Feb 23;60(4):665–673. doi: 10.1016/0092-8674(90)90669-6. [DOI] [PubMed] [Google Scholar]
- Enos A. P., Morris N. R. Mutation of a gene that encodes a kinesin-like protein blocks nuclear division in A. nidulans. Cell. 1990 Mar 23;60(6):1019–1027. doi: 10.1016/0092-8674(90)90350-n. [DOI] [PubMed] [Google Scholar]
- Hartwell L. H., Weinert T. A. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. doi: 10.1126/science.2683079. [DOI] [PubMed] [Google Scholar]
- Kuang J., Zhao J., Wright D. A., Saunders G. F., Rao P. N. Mitosis-specific monoclonal antibody MPM-2 inhibits Xenopus oocyte maturation and depletes maturation-promoting activity. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4982–4986. doi: 10.1073/pnas.86.13.4982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Labbe J. C., Picard A., Peaucellier G., Cavadore J. C., Nurse P., Doree M. Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation. Cell. 1989 Apr 21;57(2):253–263. doi: 10.1016/0092-8674(89)90963-x. [DOI] [PubMed] [Google Scholar]
- Meijer L., Arion D., Golsteyn R., Pines J., Brizuela L., Hunt T., Beach D. Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J. 1989 Aug;8(8):2275–2282. doi: 10.1002/j.1460-2075.1989.tb08353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreno S., Hayles J., Nurse P. Regulation of p34cdc2 protein kinase during mitosis. Cell. 1989 Jul 28;58(2):361–372. doi: 10.1016/0092-8674(89)90850-7. [DOI] [PubMed] [Google Scholar]
- Murray A. W., Kirschner M. W. Dominoes and clocks: the union of two views of the cell cycle. Science. 1989 Nov 3;246(4930):614–621. doi: 10.1126/science.2683077. [DOI] [PubMed] [Google Scholar]
- Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
- Oakley B. R., Morris N. R. A mutation in Aspergillus nidulans that blocks the transition from interphase to prophase. J Cell Biol. 1983 Apr;96(4):1155–1158. doi: 10.1083/jcb.96.4.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osmani A. H., Osmani S. A., Morris N. R. The molecular cloning and identification of a gene product specifically required for nuclear movement in Aspergillus nidulans. J Cell Biol. 1990 Aug;111(2):543–551. doi: 10.1083/jcb.111.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osmani S. A., Engle D. B., Doonan J. H., Morris N. R. Spindle formation and chromatin condensation in cells blocked at interphase by mutation of a negative cell cycle control gene. Cell. 1988 Jan 29;52(2):241–251. doi: 10.1016/0092-8674(88)90513-2. [DOI] [PubMed] [Google Scholar]
- Osmani S. A., May G. S., Morris N. R. Regulation of the mRNA levels of nimA, a gene required for the G2-M transition in Aspergillus nidulans. J Cell Biol. 1987 Jun;104(6):1495–1504. doi: 10.1083/jcb.104.6.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osmani S. A., Pu R. T., Morris N. R. Mitotic induction and maintenance by overexpression of a G2-specific gene that encodes a potential protein kinase. Cell. 1988 Apr 22;53(2):237–244. doi: 10.1016/0092-8674(88)90385-6. [DOI] [PubMed] [Google Scholar]
- Rosenberg A. H., Lade B. N., Chui D. S., Lin S. W., Dunn J. J., Studier F. W. Vectors for selective expression of cloned DNAs by T7 RNA polymerase. Gene. 1987;56(1):125–135. doi: 10.1016/0378-1119(87)90165-x. [DOI] [PubMed] [Google Scholar]
- Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vandré D. D., Davis F. M., Rao P. N., Borisy G. G. Distribution of cytoskeletal proteins sharing a conserved phosphorylated epitope. Eur J Cell Biol. 1986 Jun;41(1):72–81. [PubMed] [Google Scholar]
- Waring R. B., May G. S., Morris N. R. Characterization of an inducible expression system in Aspergillus nidulans using alcA and tubulin-coding genes. Gene. 1989 Jun 30;79(1):119–130. doi: 10.1016/0378-1119(89)90097-8. [DOI] [PubMed] [Google Scholar]
- Weinert T. A., Hartwell L. H. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science. 1988 Jul 15;241(4863):317–322. doi: 10.1126/science.3291120. [DOI] [PubMed] [Google Scholar]