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Regulation of DNA Synthesis by Amino Acid Limitation¹

Division of Medical Genetics, Departments of Pediatrics and Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

Mouse LM-cells growing in a low-tryptophan medium and dialyzed serum arrest at a low population density. Tryptophan was an important factor (lost on dialysis of serum), for it restored growth activity under these culture conditions. When tryptophan was added to 4-day, tryptophan-deficient, growth-arrested cultures, it caused a synchronous wave of DNA synthesis followed by partially synchronous cell division. When tryptophan was added to cultures completely starved for tryptophan for 24 hr, during which time DNA synthesis decreased to a minimum, it caused stimulation of DNA synthesis that peaked in twice the time interval as did that of tryptophan-deficient, growth-arrested cultures, and the degree of cell synchrony was not as good. The latter result could also be observed with isoleucine or leucine. It is concluded that amino acids have an effect on DNA synthesis and that the use of dialyzed serum and the manipulation of amino acid concentrations of medium can produce synchronized DNA synthesis and cell division.

¹ This work was supported by research grants to W. Sly from USPHS (GM 18475), the Woods Foundation, and the Ranken-Jordan Foundation for Crippling Diseases in Children.

² USPHS postdoctoral trainee (Grant GM 1511). Present address: Institute for Molecular Virology, St. Louis University School of Medicine, 3681 Park Avenue, St. Louis, Mo. 63110.

Received 7/25/72. Accepted 9/26/72.

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