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BUB2  -  Bub2p

Saccharomyces cerevisiae S288c

Synonyms: Cell cycle arrest protein BUB2, Mitotic check point protein BUB2, YM9796.08C, YMR055C
 
 
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High impact information on BUB2

  • How the Bfa1/Bub2 complex is regulated is not well understood [1].
  • We have also found that the MAD2 but not the BUB2 spindle checkpoint gene is required for efficient arrest of yku70Delta mutants [2].
  • When spindles are correctly oriented, Kin4 and Bub2-Bfa1 are asymmetrically localized to opposite spindle pole bodies (SPBs) [3].
  • Since components of the Bub2p checkpoint are conserved in other organisms, we propose that the position of the SPB or mammalian centrosome controls the timing of mitotic exit [4].
  • Anaphase spindle position is monitored by the BUB2 checkpoint [5].
 

Biological context of BUB2

 

Anatomical context of BUB2

  • A mutation in BUB2, a gene required for arrest of cell division in response to loss of microtubule function, diminished the delay [10].
  • In addition, a BUB2-dependent cell cycle checkpoint has been described that inhibits the mitotic exit network and cytokinesis until proper centrosome position is achieved [11].
  • In the absence of Bub2p, which is required for the spindle orientation checkpoint, this metaphase arrest was not seen in Rrp14p-depleted cells, which then arrested with multiple buds, several SPBs and binucleate mother cells [12].
 

Associations of BUB2 with chemical compounds

  • Inappropriate sister chromatid separation in nocodazole-treated bub2 cells is prevented when mitotic exit is blocked using a conditional tem1(c) mutant, indicating that the preanaphase failure in bub2 cells is a consequence of events downstream of TEM1 in the mitotic exit pathway [7].
  • In contrast, HU-induced filaments did not modulate or require BUB2, but were dependent on the GTPase Ras1p [13].
  • By random mutagenesis of Bfa1-D8(391-574) with hydroxylamine, we isolated a point mutant of D8, D8(E438K), which interacts with both Tem1p and Bub2p but cannot respond to checkpoint signals [14].
 

Physical interactions of BUB2

  • The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit [9].
  • The Nud1p-like domain of centriolin binds Bub2p, another component of the budding yeast pathway [15].
 

Regulatory relationships of BUB2

  • Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2 [16].
  • The neck localization, but not SPB localization, of Dbf2 was inhibited by the Bub2 spindle checkpoint [17].
  • The Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis [18].
  • Depletion of H2A-H2B dimers in Saccharomyces cerevisiae triggers meiotic arrest by reducing IME1 expression and activating the BUB2-dependent branch of the spindle checkpoint [19].
  • Bfa1p in association with Bub2p negatively regulates Tem1p in response to spindle damage, spindle misorientation, and DNA damage, resulting in cell cycle arrest [14].
 

Other interactions of BUB2

  • Here, we have demonstrated that introduction of bfa1 Delta suppresses the growth defects associated with the cdc5-1 mutation significantly better than that of bub2 Delta, suggesting that Bfa1 may have a previously uncharacterized role in this pathway [20].
  • Two of the identified genes, BUB2 and BUB3, have been cloned and described (M. A. Hoyt, L. Totis, and B. T. Roberts, Cell 66:507-517, 1991) [21].
  • The SPB localization of Cdc14 was significantly affected by the MEN mutations and the bub2 mutation [22].
  • IBD2 encodes a novel component of the Bub2p-dependent spindle checkpoint in the budding yeast Saccharomyces cerevisiae [23].
  • The spindle checkpoint is composed of two independent pathways, one leading to inhibition of the metaphase-to-anaphase transition by checkpoint proteins, including Mad2, and the other to inhibition of mitotic exit by Bub2 [24].
 

Analytical, diagnostic and therapeutic context of BUB2

References

  1. Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Hu, F., Wang, Y., Liu, D., Li, Y., Qin, J., Elledge, S.J. Cell (2001) [Pubmed]
  2. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Maringele, L., Lydall, D. Genes Dev. (2002) [Pubmed]
  3. Kin4 kinase delays mitotic exit in response to spindle alignment defects. Pereira, G., Schiebel, E. Mol. Cell (2005) [Pubmed]
  4. The Bub2p spindle checkpoint links nuclear migration with mitotic exit. Pereira, G., Höfken, T., Grindlay, J., Manson, C., Schiebel, E. Mol. Cell (2000) [Pubmed]
  5. Anaphase spindle position is monitored by the BUB2 checkpoint. Bloecher, A., Venturi, G.M., Tatchell, K. Nat. Cell Biol. (2000) [Pubmed]
  6. Regulation of the mitotic exit protein kinases Cdc15 and Dbf2. Visintin, R., Amon, A. Mol. Biol. Cell (2001) [Pubmed]
  7. Saccharomyces cerevisiae BUB2 prevents mitotic exit in response to both spindle and kinetochore damage. Krishnan, R., Pangilinan, F., Lee, C., Spencer, F. Genetics (2000) [Pubmed]
  8. Bifurcation of the mitotic checkpoint pathway in budding yeast. Li, R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Wang, Y., Hu, F., Elledge, S.J. Curr. Biol. (2000) [Pubmed]
  10. A delay in the Saccharomyces cerevisiae cell cycle that is induced by a dicentric chromosome and dependent upon mitotic checkpoints. Neff, M.W., Burke, D.J. Mol. Cell. Biol. (1992) [Pubmed]
  11. Search, capture and signal: games microtubules and centrosomes play. Schuyler, S.C., Pellman, D. J. Cell. Sci. (2001) [Pubmed]
  12. Yeast Rrp14p is required for ribosomal subunit synthesis and for correct positioning of the mitotic spindle during mitosis. Oeffinger, M., Fatica, A., Rout, M.P., Tollervey, D. Nucleic Acids Res. (2007) [Pubmed]
  13. Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans. Bachewich, C., Nantel, A., Whiteway, M. Mol. Microbiol. (2005) [Pubmed]
  14. The C-terminus of Bfa1p in budding yeast is essential to induce mitotic arrest in response to diverse checkpoint-activating signals. Kim, J., Jeong, J., Song, K. Genes Cells (2004) [Pubmed]
  15. A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase. Gromley, A., Jurczyk, A., Sillibourne, J., Halilovic, E., Mogensen, M., Groisman, I., Blomberg, M., Doxsey, S. J. Cell Biol. (2003) [Pubmed]
  16. Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2. Fraschini, R., Formenti, E., Lucchini, G., Piatti, S. J. Cell Biol. (1999) [Pubmed]
  17. Regulation of the localization of Dbf2 and mob1 during cell division of saccharomyces cerevisiae. Yoshida, S., Toh-e, A. Genes Genet. Syst. (2001) [Pubmed]
  18. The Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis. Lee, S.E., Jensen, S., Frenz, L.M., Johnson, A.L., Fesquet, D., Johnston, L.H. J. Cell. Sci. (2001) [Pubmed]
  19. Depletion of H2A-H2B dimers in Saccharomyces cerevisiae triggers meiotic arrest by reducing IME1 expression and activating the BUB2-dependent branch of the spindle checkpoint. Hanlon, S.E., Norris, D.N., Vershon, A.K. Genetics (2003) [Pubmed]
  20. Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network of Saccharomyces cerevisiae. Ro, H.S., Song, S., Lee, K.S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Roberts, B.T., Farr, K.A., Hoyt, M.A. Mol. Cell. Biol. (1994) [Pubmed]
  22. Mitotic exit network controls the localization of Cdc14 to the spindle pole body in Saccharomyces cerevisiae. Yoshida, S., Asakawa, K., Toh-e, A. Curr. Biol. (2002) [Pubmed]
  23. IBD2 encodes a novel component of the Bub2p-dependent spindle checkpoint in the budding yeast Saccharomyces cerevisiae. Hwang, H.S., Song, K. Genetics (2002) [Pubmed]
  24. The role of Cdc55 in the spindle checkpoint is through regulation of mitotic exit in Saccharomyces cerevisiae. Yellman, C.M., Burke, D.J. Mol. Biol. Cell (2006) [Pubmed]
  25. Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. Richardson, P.M., Zon, L.I. Oncogene (1995) [Pubmed]
  26. MAP, a protein interacting with a tumor suppressor, merlin, through the run domain. Lee, I.K., Kim, K.S., Kim, H., Lee, J.Y., Ryu, C.H., Chun, H.J., Lee, K.U., Lim, Y., Kim, Y.H., Huh, P.W., Lee, K.H., Han, S.I., Jun, T.Y., Rha, H.K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
 
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