INDIVIDUAL NUCLEI DIFFER IN THEIR SENSITIVITY TO THE CYTOPLASMIC INDUCERS OF DNA-SYNTHESIS - IMPLICATIONS FOR THE ORIGIN OF CELL-CYCLE VARIABILITY

Nuclei of multinucleate cells generally initiate DNA synthesis simulta neously, suggesting that the timing of DNA synthesis depends upon the appearance of a cytoplasmic signal. In contrast, intact nuclei from qu iescent mammalian cells initiate DNA synthesis asynchronously in cell- free extracts of Xenopus eggs, despite the common environment. Here we show that the two nuclei of permeabilized binucleate cells enter DNA synthesis coordinately in egg extracts, as they do in vivo, with diffe rent pairs of nuclei initiating replication at different times. This i ndicates that. the two nuclei of a binucleate cell are identical in th eir sensitivity to the inducers of DNA synthesis in egg extracts; this sensitivity varies in general between the nuclei of unrelated cells, The asynchrony of DNA synthesis shown by unrelated nuclei in egg extra cts is therefore not an artifact of the cell-free system but a reflect ion of genuine differences preexisting within the intact cell, Evidenc e that these differences between nuclei are responsible for a substant ial fraction of G(1) variability in Living cells is presented. (C) 199 6 Academic Press, Inc.