Open AccessHuman CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase
Author(s) -
Partha Saha,
Junjie Chen,
Kelly C. Thome,
Stephanie J. Lawlis,
Zhi Hui Hou,
Michael Hendricks,
Jeffrey D. Parvin,
Anindya Dutta
Publication year - 1998
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.18.5.2758
Subject(s) - biology , origin recognition complex , nuclear protein , dna replication , seqa protein domain , microbiology and biotechnology , dna replication factor cdt1 , s phase , replication factor c , cell nucleus , control of chromosome duplication , eukaryotic dna replication , cytoplasm , genetics , dna , gene , transcription factor
In a two-hybrid screen for proteins that interact with human PCNA, we identified and cloned a human protein (hCdc18) homologous to yeast CDC6/Cdc18 and human Orc1. Unlike yeast, in which the rapid and total destruction of CDC6/Cdc18 protein in S phase is a central feature of DNA replication, the total level of the human protein is unchanged throughout the cell cycle. Epitope-tagged protein is nuclear in G1 and cytoplasmic in S-phase cells, suggesting that DNA replication may be regulated by either the translocation of this protein between the nucleus and the cytoplasm or the selective degradation of the protein in the nucleus. Mutation of the only nuclear localization signal of this protein does not alter its nuclear localization, implying that the protein is translocated to the nucleus through its association with other nuclear proteins. Rapid elimination of the nuclear pool of this protein after the onset of DNA replication and its association with human Orc1 protein and cyclin-cdks supports its identification as human CDC6/Cdc18 protein.