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RNAi knockdown of CDC20 showed no detectable cell phenotype tends to support this conclusion. The CDC20 homologue in T. brucei could be a structural homologue but not a functional one. Our findings that there is no apparent structural homologues of MCC subunits in T. brucei genomic database and that no detectable protein was found associated with APC/C in the metaphase and beta-Mangostin chemical information dissociated from it in the anaphase of T. brucei provide a strong indication that this organism may 16483784 not have a similar mechanism of regulating metaphase-anaphase transition as observed in other eukaryotes. A similar observation has been also made in the budding yeast, in which neither the MCC subunit protein MAD2 nor the spindle assembly checkpoint complex is required for normal cell growth. This peculiarity was attributed to the persistent presence of mitotic spindles throughout the yeast cell cycle. It may not require specific spindle assembly prior to mitosis to facilitate capture of the mitotic microtubules by the kinetochores in chromosomes and biorientations of the chromosomes on the mitotic spindle. T. brucei is an even more primitive organism than yeast and may not maintain an active regulation of spindle assembly either. This postulation may explain the apparent absence of a MCC-like complex 12504917 in T. brucei. But the mechanism of activation of APC/C in triggering the metaphase to anaphase transition remains still unclear. The question whether a functional homologue of securin/ Pds1 is present in T. brucei requires still an answer. Other than the 7 subunits already identified in T. brucei APC/ C genome DB, three additional subunit proteins, APC4, AP2 and AP3, were identified in this protein complex. AP2 and AP3 cannot find homologous proteins in all the genomic databases other than those of Kinetoplastidae. Searches for common motifs in APC/C subunits such as PC repeats, cullin homology, TPR, RING H2 and WD40/IR in these two proteins also turned out negative results. AP2 and AP3 could thus be specific subunits of only the APC/C’s among the Kinetoplastidae. Among the 10 core subunits identified in T. brucei APC/C, only a knockdown of three of them, APC1, CDC27 and AP2, each resulted in an arrest of T. brucei procyclic-form cells in the metaphase. In budding yeast, 8 of the 13 APC/C subunits were found indispensible for viability. Their depletion abrogates the APC/C catalytic activity and blocks yeast cell cycle progression. The rest of the subunits are either nonessential , or their loss affects only the complex integrity or the rate of substrate binding and processing. SWM1 and CDC26 only have essential roles at restrictive temperatures in maintaining structural stability of the complex, whereas SWM1 and MND2 are essential during meiotic cell division. In S. pombe, individual knockdowns of APC14 and APC15 did not display any abnormal phenotype but the cells developed a temperature sensitive phenotype and chromosome segregation abnormalities when two proteins were mutated simultaneously or depleted with other APC components. The fact that 7 out of 10 T. brucei APC/C subunits are dispensable for cell cycle progression could mean that they have redundant structural and functional roles with the other subunits. It may require double or multiple knockdowns of these subunits to inflict a detectable phenotype. Despite all the apparent structural and functional uniqueness, T. brucei APC/C showed also some conserved functions as those observed in the other eukaryotes. The

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Author: HMTase- hmtase