CDC6 IS REGULATED BY E2F AND IS ESSENTIAL FOR DNA-REPLICATION IN MAMMALIAN-CELLS

Cdc6 has a critical regulatory role in the initiation of DNA replicati on in yeasts, but its function in mammalian cells has not been charact erized, We show here that Cdc6 is expressed selectively in proliferati ng but not quiescent mammalian cells, both In culture and within tissu es of intact animals, During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to s timulate the endogenous Cdc6 gene, Immunodepletion of Cdc6 by microinj ection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line, We conclude that expression of human Cdc6 is r egulated in response to mitogenic signals though transcriptional contr ol mechanisms Involving E2F proteins, and that Cdc6 is required for in itiation of DNA replication in mammalian cells.