MIMOSINE DIFFERENTIALLY INHIBITS DNA-REPLICATION AND CELL-CYCLE PROGRESSION IN SOMATIC-CELLS COMPARED TO EMBRYONIC-CELLS OF XENOPUS-LAEVIS

The plant amino acid mimosine has been reported to block cell cycle pr ogression and DNA replication in cultured mammalian cells, perhaps by blocking initiation. In this study, we show that mimosine does not blo ck initiation car any other step in DNA replication in embryonic cells of Xenopus laevis. Mimosine does not block DNA replication in cell-fr ee ''cycling'' extracts of Xenopus eggs, nor does it block M to S phas e transition in cell-free egg extracts released from metaphase arrest. Microinjection of mimosine into 4-cell embryos had no visible effect on development during the first 3 days after fertilization. Prior to t he midblastula transition, when the cell cycle consists of alternating S and M phases, neither chromosomal DNA replication nor replication o f microinjected plasmid DNA were inhibited by mimosine microinjected i nto cleaving Xenopus embryos. Microinjection of mimosine after the mid blastula transition, when large endogenous stockpiles of DNA replicati on components have begun to be depleted and Xenopus embryonic cells ha ve acquired G(1) and G(2) phases, still did not inhibit cell cycle pro gression or DNA replication. In marked contrast, mimosine arrested the growth of proliferating cultured Xenopus kidney epithelial A6 cells n ear the G(1)/S boundary. We conclude that mimosine appears to block DN A replication and cell cycle progression in somatic cells, but has no apparent effect in rapidly dividing Xenopus embryonic cells. (C) 1995 Academic Press, Inc.