Chromosoma

, Volume 113, Issue 4, pp 177–187

The Drosophila meiotic kleisin C(2)M functions before the meiotic divisions

  • Doris Heidmann
  • Susann Horn
  • Stefan Heidmann
  • Alexander Schleiffer
  • Kim Nasmyth
  • Christian F. Lehner
Research Article

Abstract

Stepwise and regionally controlled resolution of sister chromatid cohesion is thought to be crucial for faithful chromosome segregation during meiotic divisions. In yeast, the meiosis-specific α-kleisin subunit of the cohesin complex, Rec8, is protected from cleavage by separase but only during meiosis I and specifically within the pericentromeric region. While the Drosophila genome does not contain an obvious Rec8 orthologue, as other animal and plant genomes, it includes c(2)M, which encodes a distant α-kleisin family member involved in female meiosis. C(2)M associates in vivo with the Smc3 cohesin subunit, as previously shown for yeast Rec8. In contrast to Rec8, however, C(2)M accumulates predominantly after the pre-meiotic S-phase. Moreover, after association with the synaptonemal complex, it disappears again and cannot be detected on meiotic chromosomes by metaphase I. C(2)M cleavage fragments are not observed during completion of the meiotic divisions, and mutations within putative separase cleavage sites do not interfere with meiotic chromosome segregation. Therefore, C(2)M appears to function within the synaptonemal complex during prophase I but possibly not thereafter. This suggests that C(2)M may not confer sister chromatid cohesion needed for meiosis I and II chromosome segregation.

References

  1. Anderson DE, Losada A, Erickson HP, Hirano T (2002) Condensin and cohesin display different arm conformations with characteristic hinge angles. J Cell Biol 156:419–424CrossRefPubMedGoogle Scholar
  2. Arumugam P, Gruber S, Tanaka K, Haering CH, Mechtler K, Nasmyth K (2003) ATP hydrolysis is required for cohesin’s association with chromosomes. Curr Biol 13:1941–1953CrossRefPubMedGoogle Scholar
  3. Bickel SE, Orr-Weaver TL, Balicky EM (2002) The sister-chromatid cohesion protein ORD is required for chiasma maintenance in Drosophila oocytes. Curr Biol 12:925–929CrossRefPubMedGoogle Scholar
  4. Brown NH, Kafatos FC (1988) Functional cDNA libraries from Drosophila embryos. J Mol Biol 203:425–437PubMedGoogle Scholar
  5. Buonomo SB, Clyne RK, Fuchs J, Loidl J, Uhlmann F, Nasmyth K (2000) Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell 103:387–398CrossRefPubMedGoogle Scholar
  6. Cai X, Dong F, Edelmann RE, Makaroff CA (2003) The Arabidopsis SYN1 cohesin protein is required for sister chromatid arm cohesion and homologous chromosome pairing. J Cell Sci 116:2999–3007CrossRefPubMedGoogle Scholar
  7. Calvi BR, Lilly MA (2004) Fluorescent BrdU labeling and nuclear flow sorting of the Drosophila ovary. Methods Mol Biol 247:203–213PubMedGoogle Scholar
  8. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K (1998) An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93:1067–1076CrossRefPubMedGoogle Scholar
  9. Edgar BA, Sprenger F, Duronio RJ, Leopold P, O’Farrell PH (1994) Distinct molecular mechanisms regulate cell cycle timing at successive stages of Drosophila embryogenesis. Genes Dev 8:440–452PubMedGoogle Scholar
  10. Eijpe M, Offenberg H, Jessberger R, Revenkova E, Heyting C (2003) Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. J Cell Biol 160:657–670CrossRefPubMedGoogle Scholar
  11. Funabiki H, Yamano H, Kumada K, Nagao K, Hunt T, Yanagida M (1996) Cut2 proteolysis required for sister-chromatid separation in fission yeast. Nature 381:438–441CrossRefPubMedGoogle Scholar
  12. Golic MM, Rong YS, Petersen RB, Lindquist SL, Golic KG (1997) FLP-mediated DNA mobilization to specific target sites in Drosophila chromosomes. Nucleic Acids Res 25:3665–3671CrossRefPubMedGoogle Scholar
  13. Gruber S, Haering CH, Nasmyth K (2003) Chromosomal cohesin forms a ring. Cell 112:765–777CrossRefPubMedGoogle Scholar
  14. Haering CH, Lowe J, Hochwagen A, Nasmyth K (2002) Molecular architecture of SMC proteins and the yeast cohesin complex. Mol Cell 9:773–788CrossRefPubMedGoogle Scholar
  15. Herzig A, Lehner CF, Heidmann S (2002) Proteolytic cleavage of the THR subunit during anaphase limits Drosophila separase function. Genes Dev 16:2443–2454CrossRefPubMedGoogle Scholar
  16. Hong A, Lee-Kong S, Iida T, Sugimura I, Lilly MA (2003) The p27cip/kip ortholog dacapo maintains the Drosophila oocyte in prophase of meiosis I. Development 130:1235–1242CrossRefPubMedGoogle Scholar
  17. Jacobs HW, Knoblich JA, Lehner CF (1998) Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B. Genes Dev 12:3741–3751PubMedGoogle Scholar
  18. Jacobs HW, Richter DO, Venkatesh TR, Lehner CF (2002) Completion of mitosis requires neither fzr/rap nor fzr2, a male germline-specific Drosophila Cdh1 homolog. Curr Biol 12:1435–1441CrossRefPubMedGoogle Scholar
  19. Jäger H, Herzig A, Lehner CF, Heidmann S (2001) Drosophila separase is required for sister chromatid separation and binds to PIM and THR. Genes Dev 15:2572–2584CrossRefPubMedGoogle Scholar
  20. Kerrebrock AW, Miyazaki WY, Birnby D, Orr-Weaver TL (1992) The Drosophila mei-S322 gene promotes sister chromatid cohesion in meiosis following kinetochore differentiation. Genetics 130:827–841PubMedGoogle Scholar
  21. Kerrebrock AW, Moore DP, Wu JS, Orr-Weaver TL (1995) mei-S322, a Drosophila protein required for sister-chromatid cohesion, can localize to meiotic centromere regions. Cell 83:247–256CrossRefPubMedGoogle Scholar
  22. Kitajima TS, Miyazaki Y, Yamamoto M, Watanabe Y (2003a) Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast. EMBO J 22:5643–5653CrossRefPubMedGoogle Scholar
  23. Kitajima TS, Yokobayashi S, Yamamoto M, Watanabe Y (2003b) Distinct cohesin complexes organize meiotic chromosome domains. Science 300:1152–1155CrossRefPubMedGoogle Scholar
  24. Kitajima TS, Kawashima SA, Watanabe Y (2004) The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427:510–517CrossRefPubMedGoogle Scholar
  25. Klein F, Mahr P, Galova M, Buonomo SB, Michaelis C, Nairz K, Nasmyth K (1999) A central role for cohesins in sister chromatid cohesion, formation of axial elements, and recombination during yeast meiosis. Cell 98:91–103CrossRefPubMedGoogle Scholar
  26. Lee J, Iwai T, Yokota T, Yamashita M (2003) Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis. J Cell Sci 116:2781–2790CrossRefPubMedGoogle Scholar
  27. Leismann O, Lehner CF (2003) Drosophila securin destruction involves a D-box and a KEN-box and promotes anaphase in parallel with Cyclin A degradation. J Cell Sci 116:2453–2460CrossRefPubMedGoogle Scholar
  28. Leismann O, Herzig A, Heidmann S, Lehner CF (2000) Degradation of Drosophila PIM regulates sister chromatid separation during mitosis. Genes Dev 14:2192–2205CrossRefPubMedGoogle Scholar
  29. Losada A, Hirano M, Hirano T (2002) Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes Dev 16:3004–3016CrossRefPubMedGoogle Scholar
  30. Manheim EA, McKim KS (2003) The Synaptonemal complex component C(2)M regulates meiotic crossing over in Drosophila. Curr Biol 13:276–285CrossRefPubMedGoogle Scholar
  31. Marston AL, Tham WH, Shah H, Amon A (2004) A genome-wide screen identifies genes required for centromeric cohesion. Science 303:1367–1370CrossRefPubMedGoogle Scholar
  32. Meyer CA, Kramer I, Dittrich R, Marzodko S, Emmerich J, Lehner CF (2002) Drosophila p27Dacapo expression during embryogenesis is controlled by a complex regulatory region independent of cell cycle progression. Development 129:319–328PubMedGoogle Scholar
  33. Miyazaki WY, Orr-Weaver TL (1992) Sister-chromatid misbehavior in Drosophila ord mutants. Genetics 132:1047–1061PubMedGoogle Scholar
  34. Moore DP, Page AW, Tang TT, Kerrebrock AW, Orr-Weaver TL (1998) The cohesion protein MEI-S332 localizes to condensed meiotic and mitotic centromeres until sister chromatids separate. J Cell Biol 140:1003–1012CrossRefPubMedGoogle Scholar
  35. Page SL, Hawley RS (2001) c(3)G encodes a Drosophila synaptonemal complex protein. Genes Dev 15:3130–3143CrossRefPubMedGoogle Scholar
  36. Page AW, Orr-Weaver TL (1997) Activation of the meiotic divisions in Drosophila oocytes. Dev Biol 183:195–207CrossRefPubMedGoogle Scholar
  37. Parisi S, McKay MJ, Molnar M, Thompson MA, van der Spek PJ, van Drunen-Schoenmaker E, Kanaar R, Lehmann E, Hoeijmakers JH, Kohli J (1999) Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fission yeast to humans. Mol Cell Biol 19:3515–3528PubMedGoogle Scholar
  38. Parra MT, Viera A, Gomez R, Page J, Benavente R, Santos JL, Rufas JS, Suja JA (2004) Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetochores during mouse meiosis I. J Cell Sci 117:1221–1234CrossRefPubMedGoogle Scholar
  39. Pasierbek P, Jantsch M, Melcher M, Schleiffer A, Schweizer D, Loidl J (2001) A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes Dev 15:1349–1360CrossRefPubMedGoogle Scholar
  40. Petronczki M, Siomos MF, Nasmyth K (2003) Un menage a quatre: the molecular biology of chromosome segregation in meiosis. Cell 112:423–440CrossRefPubMedGoogle Scholar
  41. Rabitsch KP, Gregan J, Schleiffer A, Javerzat JP, Eisenhaber F, Nasmyth K (2004) Two fission yeast homologs of Drosophila mei-S332 are required for chromosome segregation during meiosis I and II. Curr Biol 14:287–301CrossRefPubMedGoogle Scholar
  42. Schleiffer A, Kaitna S, Maurer-Stroh S, Glotzer M, Nasmyth K, Eisenhaber F (2003) Kleisins: a superfamily of bacterial and eukaryotic SMC protein partners. Mol Cell 11:571–575CrossRefPubMedGoogle Scholar
  43. Spradling AC (1993) Developmental genetics of oogenesis. In: Bate M, Martinez Arias A (eds) The development of Drosophila melanogaster, vol 1. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 1–70Google Scholar
  44. Sullivan M, Hornig NC, Porstmann T, Uhlmann F (2004) Studies on substrate recognition by the budding yeast separase. J Biol Chem 279:1191–1196CrossRefPubMedGoogle Scholar
  45. Sumara I, Vorlaufer E, Stukenberg PT, Kelm O, Redemann N, Nigg EA, Peters JM (2002) The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol Cell 9:515–525CrossRefPubMedGoogle Scholar
  46. Theurkauf WE (1994) Immunofluorescence analysis of the cytoskeleton during oogenesis and early embryogenesis. Methods Cell Biol 44:489–505PubMedGoogle Scholar
  47. Uhlmann F, Nasmyth K (1998) Cohesion between sister chromatids must be established during DNA replication. Curr Biol 8:1095–1101CrossRefPubMedGoogle Scholar
  48. Uhlmann F, Wernic D, Poupart MA, Koonin EV, Nasmyth K (2000) Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103:375–386CrossRefPubMedGoogle Scholar
  49. Waizenegger IC, Hauf S, Meinke A, Peters JM (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103:399–410CrossRefPubMedGoogle Scholar
  50. Waizenegger I, Gimenez-Abian JF, Wernic D, Peters JM (2002) Regulation of human separase by securin binding and autocleavage. Curr Biol 12:1368–1378CrossRefPubMedGoogle Scholar
  51. Warren WD, Steffensen S, Lin E, Coelho P, Loupart M, Cobbe N, Lee JY, McKay MJ, Orr-Weaver T, Heck MM, Sunkel CE (2000) The Drosophila RAD21 cohesin persists at the centromere region in mitosis. Curr Biol 10:1463–1466CrossRefPubMedGoogle Scholar
  52. Watanabe Y, Nurse P (1999) Cohesin Rec8 is required for reductional chromosome segregation at meiosis. Nature 400:461–464CrossRefPubMedGoogle Scholar
  53. Watanabe Y, Yokobayashi S, Yamamoto M, Nurse P (2001) Pre-meiotic S phase is linked to reductional chromosome segregation and recombination. Nature 409:359–363CrossRefPubMedGoogle Scholar
  54. Weitzer S, Lehane C, Uhlmann F (2003) A model for ATP hydrolysis-dependent binding of cohesin to DNA. Curr Biol 13:1930–1940CrossRefPubMedGoogle Scholar
  55. Zou H, McGarry TJ, Bernal T, Kirschner MW (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285:418–422CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Doris Heidmann
    • 1
  • Susann Horn
    • 1
  • Stefan Heidmann
    • 1
  • Alexander Schleiffer
    • 2
  • Kim Nasmyth
    • 2
  • Christian F. Lehner
    • 1
  1. 1.Department of GeneticsUniversity of BayreuthBayreuthGermany
  2. 2.Research Institute of Molecular Pathology (IMP)ViennaAustria

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