Advertisement

Chromosoma

, Volume 112, Issue 7, pp 323–330 | Cite as

TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis

  • Kaarina Reini
  • Lahja Uitto
  • David Perera
  • Peter B. Moens
  • Raimundo Freire
  • Juhani E. SyväojaEmail author
Research Article

Abstract

Topoisomerase IIβ binding protein 1 (TopBP1), previously shown to localise to sites of DNA damage and to stalled replication forks, has been implicated in DNA replication and in DNA damage response. In this work we showed that TopBP1 was localised in structures other than stalled replication forks. In late mitosis TopBP1 localises to centrosomes in a manner similar to other DNA damage response proteins such as BRCA1 and p53. Spindle checkpoint activation does not affect this centrosomal localisation. Moreover, in the testis, we detected high levels of TopBP1 associated with meiotic prophase chromosome cores and the X–Y pair. Together, these data suggest a direct role of TopBP1 during both mitosis and meiotic prophase I.

Keywords

Synaptonemal Complex Nocodazole Meiotic Recombination Spindle Pole Meiotic Prophase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was funded by grants from the Academy of Finland and the Cancer Society of Finland. R.F. is supported by FIS (Fondo de Investigaciones Sanitarias) (01/1624) and FUNCIS (Fundación Canaria de Investigación Sanitaria) (PI 45/00) grants. D.P. is supported by a predoctoral fellowship from the Spanish Ministry of Education and Culture. P.B.M is supported by NSERC of Canada. We thank M. Kallio for helpful advice, and H. Pospiech and D. Kaska for editing the manuscript.

References

  1. Bailly E, Doree M, Nurse P, Bornens M (1989) p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. EMBO J 8:3985–3995PubMedGoogle Scholar
  2. Bailly E, Pines J, Hunter T, Bornens M (1992) Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome. J Cell Sci 101:529–545PubMedGoogle Scholar
  3. Deng CX (2002) Roles of BRCA1 in centrosome duplication. Oncogene 21:6222–6227CrossRefPubMedGoogle Scholar
  4. Dobson MJ, Pearlman RE, Karaiskakis A, Spyropoulos B, Moens PB (1994) Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. J Cell Sci 107:2749–2760 PubMedGoogle Scholar
  5. Freire R, Murguia JR, Tarsounas M, Lowndes NF, Moens PB, Jackson SP (1998) Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis. Genes Dev 12:2560–2573PubMedGoogle Scholar
  6. Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF (1996) Abnormal centrosome amplification in the absence of p53. Science 271:1744–1747PubMedGoogle Scholar
  7. Garcia-Diaz M, Dominguez O, Lopez-Fernandez LA, de Lera LT, Saniger ML, Ruiz JF, Parraga M, Garcia-Ortiz MJ, Kirchhoff T, del Mazo J et al (2000) DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a potential role in meiosis. J Mol Biol 301:851–867PubMedGoogle Scholar
  8. Gatti M, Smith DA, Baker BS (1983) A gene controlling condensation of heterochromatin in Drosophila melanogaster. Science 221:83–85PubMedGoogle Scholar
  9. Greer DA, Besley BDA, Kennedy KB, Davey S (2003) hRad9 rapidly binds DNA containing double-strand breaks and is required for damage-dependent topoisomerase IIβ binding protein 1 focus formation. Cancer Res 63:4829–4835PubMedGoogle Scholar
  10. Hinchcliffe EH, Miller FJ, Charm M, Khodjakov A, Sluder G (2001) Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291:1547–1550CrossRefPubMedGoogle Scholar
  11. Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M (2002) Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response. J Biol Chem 277:3599–3605CrossRefPubMedGoogle Scholar
  12. Hsu L-C, White RL (1998) BRCA1 is associated with the centrosome during mitosis. Proc Natl Acad Sci U S A 95:12983–12988CrossRefPubMedGoogle Scholar
  13. Hsu L-C, Doan TP, White RL (2001) Identification of a γ-tubulin-binding domain in BRCA1. Cancer Res 61:7713–7718PubMedGoogle Scholar
  14. Kamel D, Mackey ZB, Sjoblom T, Walter CA, McCarrey JR, Uitto L, Palosaari H, Lahdetie J, Tomkinson AE, Syväoja JE (1997) Role of deoxyribonucleic acid polymerase epsilon in spermatogenesis in mice. Biol Reprod 57:1367–1374PubMedGoogle Scholar
  15. Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ (2000) Probing spindle assembly mechanisms with monastrol, a small molecular inhibitor of the mitotic kinesin, Eg5. J Cell Biol 150:975–988CrossRefPubMedGoogle Scholar
  16. Keegan K, Holtzman D, Plug A, Christenson E, Brainerd E, Flaggs G, Bently N, Taylor E (1996) The ATR and ATM protein kinases associate with different sites along meiotically paired chromosomes. Genes Dev 10:2423–2437PubMedGoogle Scholar
  17. Larson JS, Tonkinson JL, Lai MT (1997) A BRCA1 mutant alters G2-M cell cycle control in human mammary epithelial cells. Cancer Res 57:3351–3355PubMedGoogle Scholar
  18. Mahadevaiah SK, Turner JMA, Baudat F, Rogakou EP, de Boer P, Blanco-Rodriguez J, Jasin M, Keeney S, Bonner WM, Burgoyne PS (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27:271–276CrossRefPubMedGoogle Scholar
  19. Manke IA, Lowery DM, Nguyen A, Yaffe MB (2003) BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302:579–580CrossRefPubMedGoogle Scholar
  20. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ (1999) Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286:971–974CrossRefPubMedGoogle Scholar
  21. Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE (2001) BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem 276:30399–30406CrossRefPubMedGoogle Scholar
  22. Moens PB, Tarsounas M, Morita T, Habu T, Rottinghaus ST, Freire R, Jackson SP, Barlow C, Wynshaw-Boris A (1999) The association of ATR protein with mouse meiotic chromosome cores. Chromosoma 108:95–102CrossRefPubMedGoogle Scholar
  23. Morris VB, Brammal J, Noble J, Reddel R (2000) p53 localises to the centrosomes and spindles of the mitotic cells in the embryonic chick epiblast, human cell lines, and a human primary culture: an immunofluorescence study. Exp Cell Res 256:122–130CrossRefPubMedGoogle Scholar
  24. Musacchio A, Hardwick KG (2002) The spindle checkpoint: structural insights into dynamic signalling. Nat Rev Mol Cell Biol 3:731–741CrossRefPubMedGoogle Scholar
  25. Niwa J, Ishigaki S, Doyu M, Suzuki T, Tanaka K, Sobue G (2001) A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase activity. Biochem Biophys Res Commun 281:706–713CrossRefPubMedGoogle Scholar
  26. Ogi T, Mimura J, Hikida M, Fujimoto H, Fujii-Kuriyama Y, Ohmori H (2001) Expression of human and mouse genes encoding pol kappa: testis-specific developmental regulation and AhR-dependent inducible transcription. Genes Cells 6:943–953CrossRefPubMedGoogle Scholar
  27. Parraga M, del Mazo J (2000) XYbp, a novel RING-finger protein, is a component of the XY body of spermatocytes and centrosomes. Mech Dev 90:95–101PubMedGoogle Scholar
  28. Perera D, Perez-Hidalgo L, Moens PB, Reini K, Lakin N, Syväoja JE, San-Segundo PA, Freire R (2004) TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint. Mol Biol Cell 15:1568–1579CrossRefPubMedGoogle Scholar
  29. Piel M, Nordberg J, Euteneuer U, Bornens M (2001) Centrosome-dependent exit of cytokinesis in animal cells. Science 291:1550–1553CrossRefPubMedGoogle Scholar
  30. Plug AW, Clairmont CA, Sapi E, Ashley T, Sweasy JB (1997) Evidence for a role for DNA polymerase beta in mammalian meiosis. Proc Natl Acad Sci U S A 94:1327–1331CrossRefPubMedGoogle Scholar
  31. Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88:265–275PubMedGoogle Scholar
  32. St. Onge RB, Besley BDA, Pelley JL, Davey S (2003) A role for the phosphorylation of hRad9 in checkpoint signaling. J Biol Chem 278:26620–26628CrossRefPubMedGoogle Scholar
  33. Tarapore P, Fukasawa K (2002) Loss of p53 and centrosome hyperamplification. Oncogene 21:6234–6240CrossRefPubMedGoogle Scholar
  34. Tarapore P, Horn HF, Tokuyama Y, Fukasawa K (2001a) Direct regulation of the centrosome duplication cycle by the p53–p21Waf1/Cip1 pathway. Oncogene 20:3173–3184CrossRefPubMedGoogle Scholar
  35. Tarapore P, Tokuyama Y, Horn HF, Fukasawa K (2001b) Difference in the centrosome duplication regulatory activity among p53 “hot spot” mutants: potential role of Ser 315 phosphorylation-dependent centrosome binding of p53. Oncogene 20:6851–6863CrossRefPubMedGoogle Scholar
  36. Van Hatten RA, Tutter AV, Holway AH, Khederian AM, Walter JC, Michael WM (2002) The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication. J Cell Biol 159:541–547CrossRefPubMedGoogle Scholar
  37. Waters JC, Chen R-H, Murray AW, Salmon ED (1998) Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol 141:1181–1191PubMedGoogle Scholar
  38. Xu X, Weaver Z, Linke SP, Li C, Gotay J, Wang X-W, Harris CC, Ried T, Deng C-X (1999) Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol Cell 3:389–395PubMedGoogle Scholar
  39. Xu Z-X, Timanova-Atanasova A, Zhao R-X, Chang K-S (2003) PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Mol Cell Biol 23:4247–4256CrossRefPubMedGoogle Scholar
  40. Yamamoto RR, Axton JM, Yamamoto Y, Saunders RDC, Glover DM, Henderson DS (2000) The Drosophila mus101 gene, which links DNA repair, replication and condensation of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus domains. Genetics 156:711–721PubMedGoogle Scholar
  41. Yamane K, Tsuruo T (1999) Conserved BRCT regions of TopBP1 and the tumor suppressor protein BRCA1 bind strand breaks and termini of DNA. Oncogene 18:5194–5203CrossRefPubMedGoogle Scholar
  42. Yamane K, Kawabata M, Tsuruo T (1997) A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator. Eur J Biochem 250:794–799PubMedGoogle Scholar
  43. Yamane K, Wu X, Chen J (2002) A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Mol Cell Biol 22:555–566CrossRefPubMedGoogle Scholar
  44. Yamane K, Chen J, Kinsella TJ (2003) Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint. Cancer Res 63:3049–3053PubMedGoogle Scholar
  45. Yu X, Chini CC, He M, Mer G, Chen J (2003) The BRCT domain is a phospho-protein binding domain. Science 302:579–580CrossRefPubMedGoogle Scholar
  46. Zhou B-BS, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408:433–439CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Kaarina Reini
    • 1
  • Lahja Uitto
    • 1
  • David Perera
    • 2
  • Peter B. Moens
    • 3
  • Raimundo Freire
    • 2
  • Juhani E. Syväoja
    • 1
    • 4
    Email author
  1. 1.Biocenter Oulu and Department of BiochemistryUniversity of OuluFinland
  2. 2.Hospital Universitario de CanariasUnidad de investigaciónTenerifeSpain
  3. 3.Department of BiologyYork UniversityDownsviewCanada
  4. 4.Department of BiologyUniversity of JoensuuJoensuuFinland

Personalised recommendations