MAMMALIAN BUB1 PROTEIN-KINASES - MAP POSITIONS AND IN-VIVO EXPRESSION

The spindle assembly checkpoint modulates the timing of anaphase initi ation in mitotic cells containing improperly aligned chromosomes and i ncreases the probability of successful delivery of a euploid chromosom e set to each daughter cell. We have characterized cDNA sequences from several organisms with highly significant predicted protein sequence homologies to Saccharomyces cerevisiae Bub1p, a protein required for f unction of the spindle assembly checkpoint in budding yeast. The local ization of mouse and human orthologs is in agreement with known conser vation of synteny. Mouse backcross mapping data indicate that the muri ne gene resides on chromosome 2 near IL1A, 73 cM from the mouse centro mere. Radiation hybrid mapping data indicate that the human locus exhi bits linkage to microsatellite marker D2S176, which is located within 10 cM of human IL1A. Multiple-tissue Northern analysis indicates conse rvation of expression pattern in mouse and human with markedly high mR NA levels in testis. Northern analysis of two different spindle assemb ly checkpoint protein gene products from human, BUB1 and MADE, reveals an expression pattern with common tissue distribution consistent with roles in a common pathway. In addition, we demonstrate that an mRNA f ound to accumulate in a rat fibroblast cell transformation system enco des rat BUB1, and we find that rat BUB1 mRNA accumulation correlates w ith the proliferation status of cells in culture, (C) 1997 Academic Pr ess.