Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1994 May 15;13(10):2399–2410. doi: 10.1002/j.1460-2075.1994.tb06524.x

Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes.

N Furuno 1, M Nishizawa 1, K Okazaki 1, H Tanaka 1, J Iwashita 1, N Nakajo 1, Y Ogawa 1, N Sagata 1
PMCID: PMC395105  PMID: 8194530

Abstract

Meiosis is characterized by the absence of DNA replication between the two successive divisions. In Xenopus eggs, the ability to replicate DNA develops during meiotic maturation, but is normally suppressed until fertilization. Here we show that development of the DNA-replicating ability depends on new protein synthesis during meiosis I, and that mere ablation of the endogenous c-mos product Mos allows maturing oocytes to enter interphase and replicate DNA just after meiosis I. Moreover, we demonstrate that during normal maturation cdc2 kinase undergoes precocious inactivation in meiosis I and then premature reactivation before meiosis II; importantly, this premature cdc2 reactivation absolutely requires Mos function and its direct inhibition by a dominant-negative cdc2 mutant also results in nuclear reformation and DNA replication immediately after meiosis I. These findings indicate that suppression of DNA replication during meiotic divisions in Xenopus oocytes is accomplished by the Mos-mediated premature reactivation of cdc2 kinase. We suggest that these mechanisms for suppressing DNA replication may be specific for meiosis in animal oocytes, and that the ultimate biological function, including the well known cytostatic factor activity, of Mos during meiotic maturation may be to prevent undesirable DNA replication or parthenogenetic activation before fertilization.

Full text

PDF
2410

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benbow R. M., Ford C. C. Cytoplasmic control of nuclear DNA synthesis during early development of Xenopus laevis: a cell-free assay. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2437–2441. doi: 10.1073/pnas.72.6.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blow J. J., Laskey R. A. A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature. 1988 Apr 7;332(6164):546–548. doi: 10.1038/332546a0. [DOI] [PubMed] [Google Scholar]
  3. Clarke H. J., Rossant J., Masui Y. Suppression of chromosome condensation during meiotic maturation induces parthenogenetic development of mouse oocytes. Development. 1988 Sep;104(1):97–103. doi: 10.1242/dev.104.1.97. [DOI] [PubMed] [Google Scholar]
  4. Daar I., Paules R. S., Vande Woude G. F. A characterization of cytostatic factor activity from Xenopus eggs and c-mos-transformed cells. J Cell Biol. 1991 Jul;114(2):329–335. doi: 10.1083/jcb.114.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dabauvalle M. C., Doree M., Bravo R., Karsenti E. Role of nuclear material in the early cell cycle of Xenopus embryos. Cell. 1988 Feb 26;52(4):525–533. doi: 10.1016/0092-8674(88)90465-5. [DOI] [PubMed] [Google Scholar]
  6. Draetta G. Cdc2 activation: the interplay of cyclin binding and Thr161 phosphorylation. Trends Cell Biol. 1993 Sep;3(9):287–289. doi: 10.1016/0962-8924(93)90001-h. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Ferrell J. E., Jr, Wu M., Gerhart J. C., Martin G. S. Cell cycle tyrosine phosphorylation of p34cdc2 and a microtubule-associated protein kinase homolog in Xenopus oocytes and eggs. Mol Cell Biol. 1991 Apr;11(4):1965–1971. doi: 10.1128/mcb.11.4.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freeman R. S., Pickham K. M., Kanki J. P., Lee B. A., Pena S. V., Donoghue D. J. Xenopus homolog of the mos protooncogene transforms mammalian fibroblasts and induces maturation of Xenopus oocytes. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5805–5809. doi: 10.1073/pnas.86.15.5805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gabrielli B. G., Roy L. M., Maller J. L. Requirement for Cdk2 in cytostatic factor-mediated metaphase II arrest. Science. 1993 Mar 19;259(5102):1766–1769. doi: 10.1126/science.8456304. [DOI] [PubMed] [Google Scholar]
  11. Galas S., Barakat H., Dorée M., Picard A. A nuclear factor required for specific translation of cyclin B may control the timing of first meiotic cleavage in starfish oocytes. Mol Biol Cell. 1993 Dec;4(12):1295–1306. doi: 10.1091/mbc.4.12.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gard D. L. Microtubule organization during maturation of Xenopus oocytes: assembly and rotation of the meiotic spindles. Dev Biol. 1992 Jun;151(2):516–530. doi: 10.1016/0012-1606(92)90190-r. [DOI] [PubMed] [Google Scholar]
  13. Gerhart J., Wu M., Kirschner M. Cell cycle dynamics of an M-phase-specific cytoplasmic factor in Xenopus laevis oocytes and eggs. J Cell Biol. 1984 Apr;98(4):1247–1255. doi: 10.1083/jcb.98.4.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gurdon J. B. On the origin and persistence of a cytoplasmic state inducing nuclear DNA synthesis in frogs' eggs. Proc Natl Acad Sci U S A. 1967 Aug;58(2):545–552. doi: 10.1073/pnas.58.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haccard O., Sarcevic B., Lewellyn A., Hartley R., Roy L., Izumi T., Erikson E., Maller J. L. Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase. Science. 1993 Nov 19;262(5137):1262–1265. doi: 10.1126/science.8235656. [DOI] [PubMed] [Google Scholar]
  16. Heald R., McLoughlin M., McKeon F. Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Cell. 1993 Aug 13;74(3):463–474. doi: 10.1016/0092-8674(93)80048-j. [DOI] [PubMed] [Google Scholar]
  17. Herzog N. K., Singh B., Elder J., Lipkin I., Trauger R. J., Millette C. F., Goldman D. S., Wolfes H., Cooper G. M., Arlinghaus R. B. Identification of the protein product of the c-mos proto-oncogene in mouse testes. Oncogene. 1988 Aug;3(2):225–229. [PubMed] [Google Scholar]
  18. Holloway S. L., Glotzer M., King R. W., Murray A. W. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell. 1993 Jul 2;73(7):1393–1402. doi: 10.1016/0092-8674(93)90364-v. [DOI] [PubMed] [Google Scholar]
  19. Huchon D., Crozet N., Cantenot N., Ozon R. Germinal vesicle breakdown in the Xenopus laevis oocyte: description of a transient microtubular structure. Reprod Nutr Dev. 1981;21(1):135–148. doi: 10.1051/rnd:19810112. [DOI] [PubMed] [Google Scholar]
  20. Izumi T., Walker D. H., Maller J. L. Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity. Mol Biol Cell. 1992 Aug;3(8):927–939. doi: 10.1091/mbc.3.8.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jenkins T. M., Saxena J. K., Kumar A., Wilson S. H., Ackerman E. J. DNA polymerase beta and DNA synthesis in Xenopus oocytes and in a nuclear extract. Science. 1992 Oct 16;258(5081):475–478. doi: 10.1126/science.1411545. [DOI] [PubMed] [Google Scholar]
  22. Johnson R. T., Rao P. N. Mammalian cell fusion: induction of premature chromosome condensation in interphase nuclei. Nature. 1970 May 23;226(5247):717–722. doi: 10.1038/226717a0. [DOI] [PubMed] [Google Scholar]
  23. Kanki J. P., Donoghue D. J. Progression from meiosis I to meiosis II in Xenopus oocytes requires de novo translation of the mosxe protooncogene. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5794–5798. doi: 10.1073/pnas.88.13.5794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kobayashi H., Minshull J., Ford C., Golsteyn R., Poon R., Hunt T. On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis. J Cell Biol. 1991 Aug;114(4):755–765. doi: 10.1083/jcb.114.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Krek W., Nigg E. A. Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites. EMBO J. 1991 Feb;10(2):305–316. doi: 10.1002/j.1460-2075.1991.tb07951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Krek W., Nigg E. A. Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates. EMBO J. 1991 Nov;10(11):3331–3341. doi: 10.1002/j.1460-2075.1991.tb04897.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kubiak J. Z. Mouse oocytes gradually develop the capacity for activation during the metaphase II arrest. Dev Biol. 1989 Dec;136(2):537–545. doi: 10.1016/0012-1606(89)90279-0. [DOI] [PubMed] [Google Scholar]
  28. Kubiak J. Z., Weber M., de Pennart H., Winston N. J., Maro B. The metaphase II arrest in mouse oocytes is controlled through microtubule-dependent destruction of cyclin B in the presence of CSF. EMBO J. 1993 Oct;12(10):3773–3778. doi: 10.1002/j.1460-2075.1993.tb06055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kumagai A., Dunphy W. G. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell. 1991 Mar 8;64(5):903–914. doi: 10.1016/0092-8674(91)90315-p. [DOI] [PubMed] [Google Scholar]
  30. Laskey R. A., Mills A. D., Morris N. R. Assembly of SV40 chromatin in a cell-free system from Xenopus eggs. Cell. 1977 Feb;10(2):237–243. doi: 10.1016/0092-8674(77)90217-3. [DOI] [PubMed] [Google Scholar]
  31. Lorca T., Galas S., Fesquet D., Devault A., Cavadore J. C., Dorée M. Degradation of the proto-oncogene product p39mos is not necessary for cyclin proteolysis and exit from meiotic metaphase: requirement for a Ca(2+)-calmodulin dependent event. EMBO J. 1991 Aug;10(8):2087–2093. doi: 10.1002/j.1460-2075.1991.tb07741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lorca T., Labbé J. C., Devault A., Fesquet D., Capony J. P., Cavadore J. C., Le Bouffant F., Dorée M. Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase. EMBO J. 1992 Jul;11(7):2381–2390. doi: 10.1002/j.1460-2075.1992.tb05302.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Masui Y., Clarke H. J. Oocyte maturation. Int Rev Cytol. 1979;57:185–282. doi: 10.1016/s0074-7696(08)61464-3. [DOI] [PubMed] [Google Scholar]
  34. Masui Y., Markert C. L. Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool. 1971 Jun;177(2):129–145. doi: 10.1002/jez.1401770202. [DOI] [PubMed] [Google Scholar]
  35. Maxwell S. A., Arlinghaus R. B. Serine kinase activity associated with Maloney murine sarcoma virus-124-encoded p37mos. Virology. 1985 May;143(1):321–333. doi: 10.1016/0042-6822(85)90119-9. [DOI] [PubMed] [Google Scholar]
  36. Minshull J., Murray A., Colman A., Hunt T. Xenopus oocyte maturation does not require new cyclin synthesis. J Cell Biol. 1991 Aug;114(4):767–772. doi: 10.1083/jcb.114.4.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nebreda A. R., Hunt T. The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs. EMBO J. 1993 May;12(5):1979–1986. doi: 10.1002/j.1460-2075.1993.tb05847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Newport J. W., Kirschner M. W. Regulation of the cell cycle during early Xenopus development. Cell. 1984 Jul;37(3):731–742. doi: 10.1016/0092-8674(84)90409-4. [DOI] [PubMed] [Google Scholar]
  39. Nishizawa M., Furuno N., Okazaki K., Tanaka H., Ogawa Y., Sagata N. Degradation of Mos by the N-terminal proline (Pro2)-dependent ubiquitin pathway on fertilization of Xenopus eggs: possible significance of natural selection for Pro2 in Mos. EMBO J. 1993 Oct;12(10):4021–4027. doi: 10.1002/j.1460-2075.1993.tb06080.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Nishizawa M., Okazaki K., Furuno N., Watanabe N., Sagata N. The 'second-codon rule' and autophosphorylation govern the stability and activity of Mos during the meiotic cell cycle in Xenopus oocytes. EMBO J. 1992 Jul;11(7):2433–2446. doi: 10.1002/j.1460-2075.1992.tb05308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. O'Keefe S. J., Wolfes H., Kiessling A. A., Cooper G. M. Microinjection of antisense c-mos oligonucleotides prevents meiosis II in the maturing mouse egg. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7038–7042. doi: 10.1073/pnas.86.18.7038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Paules R. S., Buccione R., Moschel R. C., Vande Woude G. F., Eppig J. J. Mouse Mos protooncogene product is present and functions during oogenesis. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5395–5399. doi: 10.1073/pnas.86.14.5395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pickham K. M., Meyer A. N., Li J., Donoghue D. J. Requirement of mosXe protein kinase for meiotic maturation of Xenopus oocytes induced by a cdc2 mutant lacking regulatory phosphorylation sites. Mol Cell Biol. 1992 Jul;12(7):3192–3203. doi: 10.1128/mcb.12.7.3192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pines J. Cyclins and cyclin-dependent kinases: take your partners. Trends Biochem Sci. 1993 Jun;18(6):195–197. doi: 10.1016/0968-0004(93)90185-p. [DOI] [PubMed] [Google Scholar]
  46. Poon R. Y., Yamashita K., Adamczewski J. P., Hunt T., Shuttleworth J. The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2. EMBO J. 1993 Aug;12(8):3123–3132. doi: 10.1002/j.1460-2075.1993.tb05981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Posada J., Yew N., Ahn N. G., Vande Woude G. F., Cooper J. A. Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro. Mol Cell Biol. 1993 Apr;13(4):2546–2553. doi: 10.1128/mcb.13.4.2546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rebagliati M. R., Weeks D. L., Harvey R. P., Melton D. A. Identification and cloning of localized maternal RNAs from Xenopus eggs. Cell. 1985 Oct;42(3):769–777. doi: 10.1016/0092-8674(85)90273-9. [DOI] [PubMed] [Google Scholar]
  49. Sagata N., Daar I., Oskarsson M., Showalter S. D., Vande Woude G. F. The product of the mos proto-oncogene as a candidate "initiator" for oocyte maturation. Science. 1989 Aug 11;245(4918):643–646. doi: 10.1126/science.2474853. [DOI] [PubMed] [Google Scholar]
  50. Sagata N., Oskarsson M., Copeland T., Brumbaugh J., Vande Woude G. F. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature. 1988 Oct 6;335(6190):519–525. doi: 10.1038/335519a0. [DOI] [PubMed] [Google Scholar]
  51. Sagata N., Watanabe N., Vande Woude G. F., Ikawa Y. The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs. Nature. 1989 Nov 30;342(6249):512–518. doi: 10.1038/342512a0. [DOI] [PubMed] [Google Scholar]
  52. Shibuya E. K., Ruderman J. V. Mos induces the in vitro activation of mitogen-activated protein kinases in lysates of frog oocytes and mammalian somatic cells. Mol Biol Cell. 1993 Aug;4(8):781–790. doi: 10.1091/mbc.4.8.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  54. Smith R. C., Bement W. M., Dersch M. A., Dworkin-Rastl E., Dworkin M. B., Capco D. G. Nonspecific effects of oligodeoxynucleotide injection in Xenopus oocytes: a reevaluation of previous D7 mRNA ablation experiments. Development. 1990 Nov;110(3):769–779. doi: 10.1242/dev.110.3.769. [DOI] [PubMed] [Google Scholar]
  55. Solomon M. J., Lee T., Kirschner M. W. Role of phosphorylation in p34cdc2 activation: identification of an activating kinase. Mol Biol Cell. 1992 Jan;3(1):13–27. doi: 10.1091/mbc.3.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Surana U., Amon A., Dowzer C., McGrew J., Byers B., Nasmyth K. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J. 1993 May;12(5):1969–1978. doi: 10.1002/j.1460-2075.1993.tb05846.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Watanabe N., Vande Woude G. F., Ikawa Y., Sagata N. Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs. Nature. 1989 Nov 30;342(6249):505–511. doi: 10.1038/342505a0. [DOI] [PubMed] [Google Scholar]
  58. Weber M., Kubiak J. Z., Arlinghaus R. B., Pines J., Maro B. c-mos proto-oncogene product is partly degraded after release from meiotic arrest and persists during interphase in mouse zygotes. Dev Biol. 1991 Nov;148(1):393–397. doi: 10.1016/0012-1606(91)90347-6. [DOI] [PubMed] [Google Scholar]
  59. Yew N., Mellini M. L., Vande Woude G. F. Meiotic initiation by the mos protein in Xenopus. Nature. 1992 Feb 13;355(6361):649–652. doi: 10.1038/355649a0. [DOI] [PubMed] [Google Scholar]
  60. Young C. W., Hendler F. J., Karnofsky D. A. Synthesis of protein for DNA replication and cleavage events in the sand dollar embryo. Exp Cell Res. 1969 Nov;58(1):15–26. doi: 10.1016/0014-4827(69)90112-8. [DOI] [PubMed] [Google Scholar]
  61. Zampetti-Bosseler F., Huez G., Brachet J. Effects of several inhibitors of macromolecule synthesis upon maturation of marine invertebrate oocytes. Exp Cell Res. 1973 Apr;78(2):383–393. doi: 10.1016/0014-4827(73)90083-9. [DOI] [PubMed] [Google Scholar]
  62. van Loon A. E., Colas P., Goedemans H. J., Néant I., Dalbon P., Guerrier P. The role of cyclins in the maturation of Patella vulgata oocytes. EMBO J. 1991 Nov;10(11):3343–3349. doi: 10.1002/j.1460-2075.1991.tb04898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. van der Hoorn F. A., Spiegel J. E., Maylié-Pfenninger M. F., Nordeen S. K. A 43 kD c-mos protein is only expressed before meiosis during rat spermatogenesis. Oncogene. 1991 Jun;6(6):929–932. [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES