Laabs Tracy L, Markwardt David D, Slattery Matthew G, Newcomb Laura L, Stillman David J, Heideman Warren
School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10275-80. doi: 10.1073/pnas.1833999100. Epub 2003 Aug 22.
Saccharomyces cerevisiae cells reproduce by budding to yield a mother cell and a smaller daughter cell. Although both mother and daughter begin G1 simultaneously, the mother cell progresses through G1 more rapidly. Daughter cell G1 delay has long been thought to be due to a requirement for attaining a certain critical cell size before passing the commitment point in the cell cycle known as START. We present an alternative model in which the daughter cell-specific Ace2 transcription factor delays G1 in daughter cells. Deletion of ACE2 produces daughter cells that proceed through G1 at the same rate as mother cells, whereas a mutant Ace2 protein that is not restricted to daughter cells delays G1 equally in both mothers and daughters. The differential in G1 length between mothers and daughters requires the Cln3 G1 cyclin, and CLN3-GFP reporter expression is reduced in daughters in an ACE2-dependent manner. Specific daughter delay elements in the CLN3 promoter are required for normal daughter G1 delay, and these elements bind to an unidentified 127-kDa protein. This DNA-binding activity is enhanced by deletion of ACE2. These results support a model in which daughter cell G1 delay is determined not by cell size but by an intrinsic property of the daughter cell generated by asymmetric cell division.
酿酒酵母细胞通过出芽进行繁殖，产生一个母细胞和一个较小的子细胞。虽然母细胞和子细胞同时进入G1期，但母细胞通过G1期的速度更快。长期以来，人们一直认为子细胞G1期延迟是由于在细胞周期中通过称为START的承诺点之前需要达到一定的临界细胞大小。我们提出了一种替代模型，其中子细胞特异性Ace2转录因子延迟子细胞的G1期。删除ACE2会产生以与母细胞相同的速度通过G1期的子细胞，而不限于子细胞的突变Ace2蛋白会在母细胞和子细胞中同样延迟G1期。母细胞和子细胞之间G1期长度的差异需要Cln3 G1细胞周期蛋白，并且CLN3-GFP报告基因的表达以ACE2依赖的方式在子细胞中降低。CLN3启动子中的特定子细胞延迟元件是正常子细胞G1期延迟所必需的，并且这些元件与一种未鉴定的127 kDa蛋白结合。这种DNA结合活性通过删除ACE2而增强。这些结果支持了一种模型，其中子细胞G1期延迟不是由细胞大小决定的，而是由不对称细胞分裂产生的子细胞的内在特性决定的。
