CDC6: from DNA replication to cell cycle checkpoints and oncogenesis.
Cell division cycle 6 (CDC6) is an essential regulator of DNA replication in eukaryotic cells. Its best-characterized function is the assembly of prereplicative complexes at origins of replication during the G(1) phase of the cell division cycle. However, CDC6 also plays important roles in the activation and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis, and recent studies have unveiled its proto-oncogenic activity. CDC6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. These findings indicate that deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis.
DNA replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Luis R
LR
Borlado
Juan
J
Méndez
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000648:ultrastructure; D004249:DNA Damage; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology*; D009857:Oncogenes; D051738:Origin Recognition Complex; D012306:Risk
C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; D009687:Nuclear Proteins; D051738:Origin Recognition Complex; D000255:Adenosine Triphosphate