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. 2000 May;155(1):159–166. doi: 10.1093/genetics/155.1.159

Drosophila wee1 has an essential role in the nuclear divisions of early embryogenesis.

D Price 1, S Rabinovitch 1, P H O'Farrell 1, S D Campbell 1
PMCID: PMC1461082  PMID: 10790391

Abstract

In Drosophila, the maternally expressed mei-41 and grp genes are required for successful execution of the nuclear division cycles of early embryogenesis. In fission yeast, genes encoding similar kinases (rad3 and chk1, respectively) are components of a cell cycle checkpoint that delays mitosis by inhibitory phosphorylation of Cdk1. We have identified mutations in a gene encoding a Cdk1 inhibitory kinase, Drosophila wee1 (Dwee1). Like mei-41 and grp, Dwee1 is zygotically dispensable but is required maternally for completing the embryonic nuclear cycles. The arrest phenotype of Dwee1 mutants, as well as genetic interactions between Dwee1, grp, and mei-41 mutations, suggest that Dwee1 is functioning in the same regulatory pathway as these genes. These findings imply that inhibitory phosphorylation of Cdk1 by Dwee1 is required for proper regulation of the early syncytial cycles of embryogenesis.

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Selected References

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  1. Alphey L., Jimenez J., White-Cooper H., Dawson I., Nurse P., Glover D. M. twine, a cdc25 homolog that functions in the male and female germline of Drosophila. Cell. 1992 Jun 12;69(6):977–988. doi: 10.1016/0092-8674(92)90616-k. [DOI] [PubMed] [Google Scholar]
  2. Beamish H., Williams R., Chen P., Lavin M. F. Defect in multiple cell cycle checkpoints in ataxia-telangiectasia postirradiation. J Biol Chem. 1996 Aug 23;271(34):20486–20493. doi: 10.1074/jbc.271.34.20486. [DOI] [PubMed] [Google Scholar]
  3. Bentley N. J., Holtzman D. A., Flaggs G., Keegan K. S., DeMaggio A., Ford J. C., Hoekstra M., Carr A. M. The Schizosaccharomyces pombe rad3 checkpoint gene. EMBO J. 1996 Dec 2;15(23):6641–6651. [PMC free article] [PubMed] [Google Scholar]
  4. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  5. Campbell S. D., Sprenger F., Edgar B. A., O'Farrell P. H. Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro. Mol Biol Cell. 1995 Oct;6(10):1333–1347. doi: 10.1091/mbc.6.10.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen L., Liu T. H., Walworth N. C. Association of Chk1 with 14-3-3 proteins is stimulated by DNA damage. Genes Dev. 1999 Mar 15;13(6):675–685. doi: 10.1101/gad.13.6.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chou T. B., Perrimon N. The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics. 1996 Dec;144(4):1673–1679. doi: 10.1093/genetics/144.4.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Courtot C., Fankhauser C., Simanis V., Lehner C. F. The Drosophila cdc25 homolog twine is required for meiosis. Development. 1992 Oct;116(2):405–416. doi: 10.1242/dev.116.2.405. [DOI] [PubMed] [Google Scholar]
  9. Edgar B. A., O'Farrell P. H. Genetic control of cell division patterns in the Drosophila embryo. Cell. 1989 Apr 7;57(1):177–187. doi: 10.1016/0092-8674(89)90183-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Edgar B. A., O'Farrell P. H. The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string. Cell. 1990 Aug 10;62(3):469–480. doi: 10.1016/0092-8674(90)90012-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foe V. E., Alberts B. M. Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis. J Cell Sci. 1983 May;61:31–70. doi: 10.1242/jcs.61.1.31. [DOI] [PubMed] [Google Scholar]
  12. Fogarty P., Campbell S. D., Abu-Shumays R., Phalle B. S., Yu K. R., Uy G. L., Goldberg M. L., Sullivan W. The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity. Curr Biol. 1997 Jun 1;7(6):418–426. doi: 10.1016/s0960-9822(06)00189-8. [DOI] [PubMed] [Google Scholar]
  13. Fogarty P., Kalpin R. F., Sullivan W. The Drosophila maternal-effect mutation grapes causes a metaphase arrest at nuclear cycle 13. Development. 1994 Aug;120(8):2131–2142. doi: 10.1242/dev.120.8.2131. [DOI] [PubMed] [Google Scholar]
  14. Hammond L. E., Rudner D. Z., Kanaar R., Rio D. C. Mutations in the hrp48 gene, which encodes a Drosophila heterogeneous nuclear ribonucleoprotein particle protein, cause lethality and developmental defects and affect P-element third-intron splicing in vivo. Mol Cell Biol. 1997 Dec;17(12):7260–7267. doi: 10.1128/mcb.17.12.7260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hari K. L., Santerre A., Sekelsky J. J., McKim K. S., Boyd J. B., Hawley R. S. The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell. 1995 Sep 8;82(5):815–821. doi: 10.1016/0092-8674(95)90478-6. [DOI] [PubMed] [Google Scholar]
  16. Heinrichs V., Baker B. S. The Drosophila SR protein RBP1 contributes to the regulation of doublesex alternative splicing by recognizing RBP1 RNA target sequences. EMBO J. 1995 Aug 15;14(16):3987–4000. doi: 10.1002/j.1460-2075.1995.tb00070.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jimenez G., Yucel J., Rowley R., Subramani S. The rad3+ gene of Schizosaccharomyces pombe is involved in multiple checkpoint functions and in DNA repair. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4952–4956. doi: 10.1073/pnas.89.11.4952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnston L. A., Edgar B. A. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature. 1998 Jul 2;394(6688):82–84. doi: 10.1038/27925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kenna M., Stevens A., McCammon M., Douglas M. G. An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity. Mol Cell Biol. 1993 Jan;13(1):341–350. doi: 10.1128/mcb.13.1.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lopez-Girona A., Furnari B., Mondesert O., Russell P. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature. 1999 Jan 14;397(6715):172–175. doi: 10.1038/16488. [DOI] [PubMed] [Google Scholar]
  21. Lynch K. W., Maniatis T. Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer. Genes Dev. 1996 Aug 15;10(16):2089–2101. doi: 10.1101/gad.10.16.2089. [DOI] [PubMed] [Google Scholar]
  22. Matunis E. L., Matunis M. J., Dreyfuss G. Characterization of the major hnRNP proteins from Drosophila melanogaster. J Cell Biol. 1992 Jan;116(2):257–269. doi: 10.1083/jcb.116.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Milán M., Campuzano S., García-Bellido A. Cell cycling and patterned cell proliferation in the wing primordium of Drosophila. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):640–645. doi: 10.1073/pnas.93.2.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Neumann C. J., Cohen S. M. Sternopleural is a regulatory mutation of wingless with both dominant and recessive effects on larval development of Drosophila melanogaster. Genetics. 1996 Apr;142(4):1147–1155. doi: 10.1093/genetics/142.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. O'Connell M. J., Raleigh J. M., Verkade H. M., Nurse P. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. EMBO J. 1997 Feb 3;16(3):545–554. doi: 10.1093/emboj/16.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Peng C. Y., Graves P. R., Thoma R. S., Wu Z., Shaw A. S., Piwnica-Worms H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science. 1997 Sep 5;277(5331):1501–1505. doi: 10.1126/science.277.5331.1501. [DOI] [PubMed] [Google Scholar]
  27. Sanchez Y., Wong C., Thoma R. S., Richman R., Wu Z., Piwnica-Worms H., Elledge S. J. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science. 1997 Sep 5;277(5331):1497–1501. doi: 10.1126/science.277.5331.1497. [DOI] [PubMed] [Google Scholar]
  28. Shobuike T., Sugano S., Yamashita T., Ikeda H. Characterization of cDNA encoding mouse homolog of fission yeast dhp1+ gene: structural and functional conservation. Nucleic Acids Res. 1995 Feb 11;23(3):357–361. doi: 10.1093/nar/23.3.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sibon O. C., Laurençon A., Hawley R., Theurkauf W. E. The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Curr Biol. 1999 Mar 25;9(6):302–312. doi: 10.1016/s0960-9822(99)80138-9. [DOI] [PubMed] [Google Scholar]
  30. Sibon O. C., Stevenson V. A., Theurkauf W. E. DNA-replication checkpoint control at the Drosophila midblastula transition. Nature. 1997 Jul 3;388(6637):93–97. doi: 10.1038/40439. [DOI] [PubMed] [Google Scholar]
  31. Su T. T., Sprenger F., DiGregorio P. J., Campbell S. D., O'Farrell P. H. Exit from mitosis in Drosophila syncytial embryos requires proteolysis and cyclin degradation, and is associated with localized dephosphorylation. Genes Dev. 1998 May 15;12(10):1495–1503. doi: 10.1101/gad.12.10.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Török T., Tick G., Alvarado M., Kiss I. P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: isolation of lethals with different overgrowth phenotypes. Genetics. 1993 Sep;135(1):71–80. doi: 10.1093/genetics/135.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Walworth N. C., Bernards R. rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science. 1996 Jan 19;271(5247):353–356. doi: 10.1126/science.271.5247.353. [DOI] [PubMed] [Google Scholar]
  34. Walworth N., Davey S., Beach D. Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2. Nature. 1993 May 27;363(6427):368–371. doi: 10.1038/363368a0. [DOI] [PubMed] [Google Scholar]
  35. Wu P., Brockenbrough J. S., Metcalfe A. C., Chen S., Aris J. P. Nop5p is a small nucleolar ribonucleoprotein component required for pre-18 S rRNA processing in yeast. J Biol Chem. 1998 Jun 26;273(26):16453–16463. doi: 10.1074/jbc.273.26.16453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zeng Y., Forbes K. C., Wu Z., Moreno S., Piwnica-Worms H., Enoch T. Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature. 1998 Oct 1;395(6701):507–510. doi: 10.1038/26766. [DOI] [PubMed] [Google Scholar]

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