Malsegregation of chromosomes causes aneuploidy, which is associated with birth defects, diseases and the stage progression of cancers. The goal of this proposal is to elucidate the function of two genes, s1p1+ and mad2+, both of which play key roles in regulating the onset of anaphase to insure accurate chromosome segregation. The following aims are proposed: 1) A loss of function of s1p1+ results in a metaphase arrest. P34cdc2 kinase, spindle structure, and anaphase promoting complex (APC) will be examined in the s1p1 mutant to identify the specific mitotic event which requires the functional s1p1+. 2) mad2+ is a component of the spindle-assembly checkpoint and forms a complex with s1p1+ in vitro. To address the significance of the s1p1-mad2 complex, the nature of the complex will be examined by immunoprecipitation in vivo. A mad2 mutant defective in its binding to s1p1+ will be expressed to determine the consequence of a failure in the complex formation. 3) The overproduction of mad2+ causes a metaphase arrest. The mechanism to induce the metaphase arrest will be investigated by characterizing mutants which are resistant to the overproduction of mad2+, and examining APC and its downstream elements. 4) To test if the mad2+-dependent checkpoint is required in meiosis, an artificial mini-chromosome, which segregates accurately in wild type strains, will be introduced into a knock-out of mad2+ and the frequency of abnormal meiotic segregation will be measured.
| Ikui, Amy E; Furuya, Kanji; Yanagida, Mitsuhiro et al. (2002) Control of localization of a spindle checkpoint protein, Mad2, in fission yeast. J Cell Sci 115:1603-10 |
| Matsumoto, Sanae; Bandyopadhyay, Amitabha; Kwiatkowski, David J et al. (2002) Role of the Tsc1-Tsc2 complex in signaling and transport across the cell membrane in the fission yeast Schizosaccharomyces pombe. Genetics 161:1053-63 |
| Habu, Toshiyuki; Kim, Sang Hoon; Weinstein, Jasminder et al. (2002) Identification of a MAD2-binding protein, CMT2, and its role in mitosis. EMBO J 21:6419-28 |
| Yamada, H Y; Matsumoto, S; Matsumoto, T (2000) High dosage expression of a zinc finger protein, Grt1, suppresses a mutant of fission yeast slp1(+), a homolog of CDC20/p55CDC/Fizzy. J Cell Sci 113 ( Pt 22):3989-99 |
| Kim, S H; Lin, D P; Matsumoto, S et al. (1998) Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science 279:1045-7 |
