Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae

AUTOR(ES)

Mizunuma, Masaki

FONTE

National Academy of Sciences

RESUMO

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 Ca2+-sensitive phenotypes of the zds1Δ strain, such as the Ca2+-induced, Swe1p- and Cln2p-mediated G2 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 Ca2+ sensitivity by the sah1-1 mutation. Exogenous AdoMet transiently led the cells to G1 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.

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