Identification of the sequence responsible for the nuclear localization of human Cdc6

The Cdc6 is the essential protein for the initiation of DNA replication. Cdc6 is localized in the G1 nucleus, and abnormal nuclear localization of this protein induces irregular initiation of DNA replication. We identified here that amino acids K-57 and R-58 in the human Cdc6 protein play an important role in the nuclear localization of the protein, The fundamental features of the mechanism regulating the localization of Cdc6 seem to be maintained in yeast, Xenopus, and human, since the amino acid sequence surrounding K-57 and R-58, (S/T)PXKR(L/I), is conserved in these species. Substitution of amino acid residue S-54 with E and not Q blocked partially the nuclear localization of the protein, implying that the phosphorylation at S-54 is involved in the regulating mechanism of the cell cycle-dependent localization of Cdc6, (C) 1999 Federation of European Biochemical Societies.