Cell Division Cycle 6 (CDC6) is an approximately 62 kDa nuclear protein involved in DNA replication initiation that is expressed only in proliferating cells. Along with minichromosome maintenance (MCM) and Origin Recognition Complex (ORC), CDC6 is assembled onto chromatin to form a pre-replicative complex. In the absence of CDC6, cells fail to initiate DNA replication and undergo a "reductional" mitosis, in which the unreplicated chromosomes are randomly segregated to the spindle poles. CDC6 is activated at the G1/S phase of the cell cycle by the activity of the transcrIPPtion factor E2F3. CDC6 interacts directly with the cyclin A/Cdk2 complex, resulting in phosphorylation of CDC6 and translocation to the cytoplasm. Since down-regulation of CDC6 by Cdks restricts replication to only once per cell cycle, mutations in CDC6 may play an important role in cancer and tumorigenesis.