The Cdc6 protein is an essential component of pre-replication complexes (preRCs), which assemble at origins of DNA replication during the G1 phase of the cell cycle (1). Cdc6p and cdc18+ are unstable proteins that are essential and rate limiting for the initiation of DNA replication in Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. They participate in checkpoint controls that ensure DNA replication is completed before mitosis is initiated (2). It has been concluded that expression of Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells (3). Cdc6 is believed to be phosphorylated at Serine 54 during S phase and functions as a chromatin-bound signal that prevents reformation of prereplication complexes (4).
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