McNulty John J, Lew Daniel J
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Curr Biol. 2005 Dec 20;15(24):2190-8. doi: 10.1016/j.cub.2005.11.039.
S. cerevisiae cells must grow to a critical size in G1 in order to pass start and enter the cell cycle. A recent study proposed that in addition to the mother size control in G1, the bud must grow to a critical bud size in G2 in order to enter mitosis. Insufficient bud size would cause G2 arrest enforced by the mitotic inhibitor Swe1p, explaining previous findings that some perturbations that block bud growth also trigger Swe1p-dependent cell-cycle arrest.
We tested the critical-bud-size hypothesis. We found that halting bud growth by inactivation of the myosin Myo2p did not trigger Swe1p-dependent arrest in budded cells, even when the buds were very small. Moreover, Swe1p did not affect cell-cycle progression in unstressed cells, even when bud size was decreased by overriding G1 size control. Actin depolymerization did cause Swe1p-dependent arrest in small-budded but not large-budded cells, as previously reported. However, we found that the key determinant of cell-cycle arrest in those circumstances was not bud size, but rather the relative abundance of the Swe1p mitotic inhibitor and the mitosis-promoting cyclins.
Swe1p does not respond to insufficient bud size. Instead, actin stress empowers Swe1p to promote arrest. The effectiveness of Swe1p in promoting that arrest declines as cells progress through the cell cycle.
酿酒酵母细胞必须在G1期生长到临界大小才能通过起始点并进入细胞周期。最近的一项研究提出,除了G1期的母细胞大小控制外,芽在G2期必须生长到临界芽大小才能进入有丝分裂。芽大小不足会导致有丝分裂抑制剂Swe1p介导的G2期停滞,这解释了之前的一些发现,即一些阻碍芽生长的扰动也会触发Swe1p依赖的细胞周期停滞。
我们对临界芽大小假说进行了测试。我们发现,通过使肌球蛋白Myo2p失活来停止芽生长,并不会在出芽细胞中触发Swe1p依赖的停滞,即使芽非常小。此外,Swe1p不会影响未受应激细胞的细胞周期进程,即使通过超越G1期大小控制来减小芽大小。正如之前报道的那样,肌动蛋白解聚确实会在小芽而非大芽细胞中导致Swe1p依赖的停滞。然而,我们发现,在这些情况下细胞周期停滞的关键决定因素不是芽大小,而是有丝分裂抑制剂Swe1p和有丝分裂促进细胞周期蛋白的相对丰度。
Swe1p不会对芽大小不足做出反应。相反,肌动蛋白应激使Swe1p能够促进停滞。随着细胞在细胞周期中进展,Swe1p促进停滞的有效性会下降。