Identification of the sequence responsible for the nuclear localization ofhuman Cdc6

The Cdc6 is the essential protein for the initiation of DNA replication. Cd c6 is localized in the G1 nucleus, and abnormal nuclear localization of thi s protein induces irregular initiation of DNA replication. We identified he re that amino acids K-57 and R-58 in the human Cdc6 protein play an importa nt role in the nuclear localization of the protein, The fundamental feature s of the mechanism regulating the localization of Cdc6 seem to be maintaine d 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 o f amino acid residue S-54 with E and not Q blocked partially the nuclear lo calization of the protein, implying that the phosphorylation at S-54 is inv olved in the regulating mechanism of the cell cycle-dependent localization of Cdc6, (C) 1999 Federation of European Biochemical Societies.