sample critical review
Although the two groups propose a new role of γ-TuRC in late mitosis regulation, the model organism, the mutated proteins, mutation extent, and observations in the two papers are different, which influenced their deduction of the potential function of γ-TuRC in mitosis regulation. First, the protein mutated in Leah Vardy’s experiment is Alp4, which is one of γ-TuRC components in fission yeast (Vardy et al., 2002), while in Prigozhila’s research, γ-tubulin in Aspergillus Nidulans was mutated(Prigozhina et al., 2004). Vardy deleted a fragment of Alp4 protein, which is a severe mutation way and could cause the observed loss of γ-TuRC from SPBs and the formation of abnormal monopolar spindle. Since the monopolar spindle formed before the premature septation occurred in the mutant, directly correlating mutation of alp4 with the premature mitotic exit sounds arbitrary. The evidence to exclude the cause-and-effect relationship between defective bipolar spindle formation and disruption of late mitotic events are necessary for their speculation of the potential negative role of γ-TuRCs in late mitosis regulation. It is also worth noting that such deregulated mitosis only happens or was observed in the second mitosis in their Alp4 mutant instead of the first mitosis. Therefore, Vardy can not exclude the possibility that the observed premature septation is a secondary effect of loss of γ-TuRCs, say, a consequence of unobserved or undetectable defects accumulated in the first cell cycle either.
Compared with Vardy’s deletion of Alp4 protein, Prigozhila and colleague, however, chose a relatively mild mutation way. They only mutated two amino acids on γ-tubulin, which minimized the interference of the microtubule nucleation function of γ-tubulin on γ-TuRC. Their video also show that the bipolar spindle formed normally in the γ-tubulin mutant and can exert force on chromosomes as normal cells. In this way, they demonstrated that the observed disruption of late mitotic events did not result from the defect in spindle formation. Furthermore, the fact that premature mitotic exit happens in the first mitosis also excluded the possibility that such disruption is a consequence of defects in the previous cell cycle and demonstrated that the two-site mutation on γ-tubulin is directly responsible for the disruption of mitotic events in one cell cycle..
Both groups proved that the disruption effect of the defective γ-TuRC in their mutant is not carried out through the Mad2 checkpoint pathway, though they used different methods: Vardy showed the Mad2 activation in Alp4 mutant and Prigozhila showed that the γ-tubulin is synthetically lethal with Mad2. Because γ-TuRC do not change their localization throughout the whole cell cycle (Oakley and Akkari, 1999), Prigozhila and colleague’s implication that the mutant of γ-tubulin deregulate the mitotic events by loosing the correct spatial or temporal binding of mitotic regulator to SPB is thought-provoking and inclusive with the notion of Leah Vardy.