Mizunuma Masaki, Miyamura Kazunori, Hirata Dai, Yokoyama Hiroshi, Miyakawa Tokichi
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6086-91. doi: 10.1073/pnas.0308314101. Epub 2004 Apr 8.
S-adenosyl-l-methionine (AdoMet) is a molecule central to general metabolism, serving as a principal methyl donor for methylation of various cellular constituents. The alteration in the availability of AdoMet has profound effect on cell growth. A mutant allele of Saccharomyces cerevisiae gene SAH1 encoding S-adenosyl-l-homocysteine (AdoHcy) hydrolase, was isolated as a mutation that suppressed the Ca(2+)-sensitive phenotypes of the zds1Delta strain, such as the Ca(2+)-induced, Swe1p- and Cln2p-mediated G(2) cell-cycle arrest, and polarized bud growth. The mutation (sah1-1) led the cells to accumulate AdoMet besides AdoHcy, the substrate of Sah1p. The cells treated with exogenous AdoMet and AdoHcy had markedly decreased levels of SWE1 and CLN2 mRNA, providing the basis for the suppression of the Ca(2+) sensitivity by the sah1-1 mutation. Exogenous AdoMet transiently led the cells to G(1) cell-cycle delay whereas AdoHcy caused growth inhibition irrelevant to the cell cycle. The effect of AdoMet in inducing the cell-cycle delay was exerted in a manner independent of Met4p, an overall transcriptional activator for MET genes. Our observation provides an insight into the role played by AdoMet in cell cycle regulation.
S-腺苷-L-甲硫氨酸（AdoMet）是一般新陈代谢的核心分子，作为各种细胞成分甲基化的主要甲基供体。AdoMet可用性的改变对细胞生长有深远影响。酿酒酵母基因SAH1的一个突变等位基因编码S-腺苷-L-高半胱氨酸（AdoHcy）水解酶，作为一种抑制zds1Delta菌株钙敏感表型的突变被分离出来，如钙诱导的、Swe1p和Cln2p介导的G2期细胞周期停滞以及极化芽生长。该突变（sah1-1）导致细胞除了积累Sah1p的底物AdoHcy外，还积累AdoMet。用外源性AdoMet和AdoHcy处理的细胞中SWE1和CLN2 mRNA水平显著降低，为sah1-1突变抑制钙敏感性提供了基础。外源性AdoMet短暂导致细胞G1期细胞周期延迟，而AdoHcy导致与细胞周期无关的生长抑制。AdoMet诱导细胞周期延迟的作用是以独立于Met4p（MET基因的整体转录激活因子）的方式发挥的。我们的观察为AdoMet在细胞周期调控中的作用提供了见解。
