High impact information on Bub1

• Drosophila cells lacking either ROD or Zw10 exhibit a phenotype that is similar to that of bub1 mutants - they do not arrest in metaphase in response to spindle damage, but instead separate sister chromatids, degrade cyclin B and exit mitosis [1].
• The point of arrest corresponds to the spindle integrity checkpoint; Bub1 protein and the 3F3/2 epitope are present on the separated kinetochores and the arrest is suppressed by a bub1 mutation [2].
• We show that Bub1 kinase activity is not required for phosphorylation of 3F3/2 epitopes at prophase/prometaphase, but is needed for 3F3/2 dephosphorylation at metaphase [3].
• Chromosome fragmentation possibly leads to the significantly elevated levels of apoptosis seen in mutants.We have also investigated the relationship between Bub1 and other kinetochore components [3].
• Neither 3F3/2 dephosphorylation nor loss of Bub1 from the kinetochore is a prerequisite for anaphase entry [3].

Biological context of Bub1

• We find that mitotic cyclins are stabilized and that a spindle checkpoint protein, Bub1, localizes onto chromosomes during mitotic arrest in dup mutants [4].
• mei-41 and bub1 block mitosis at two distinct steps in response to incomplete DNA replication in Drosophila embryos [4].
• To our knowledge, this is the first report of (1) incomplete DNA replication affecting both the entry into and the exit from mitosis in a single cell cycle via different mechanisms and (2) the role of bub1 in regulating mitotic exit in response to incomplete DNA replication [4].
• Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod [5].
• To determine BubR1 function during embryogenesis, we generated a new hypomorphic semi-viable female sterile allele [6].

Other interactions of Bub1

• We further show that the localization of Bub3 to the kinetochore is disrupted by mutations in the gene encoding the Drosophila homolog of the spindle assembly checkpoint protein Bub1 [5].
• Consistently, in mono-oriented chromosomes, both kinetochores accumulate BubR1 whereas Bub1 and Mad2 only localize at the unattached kinetochore [7].
• The metaphase-like arrest of mks mutants cannot be overcome by mutations in the spindle integrity checkpoint gene bub1, confirming this surveillance pathway has to operate through the APC/C [8].
• Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components [9].

References