Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae.
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.
Mizunuma
Masaki
M
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
Miyamura
Kazunori
K
Hirata
Dai
D
Yokoyama
Hiroshi
H
Miyakawa
Tokichi
T
D043383:Adenosylhomocysteinase / Q000235:genetics; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000235:genetics; D017931:DNA Primers; D016193:G1 Phase / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012436:S-Adenosylmethionine / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D043383:Adenosylhomocysteinase; D002118:Calcium