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A human protein related to yeast Cdc6p
R S Williams1, R V Shohet, B Stillman
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Summary
Researchers identified human and Xenopus proteins related to yeast Cdc6p/cdc18, crucial for DNA replication initiation and cell cycle checkpoints. Human p62(cdc6) expression correlates with cell cycle reentry and DNA replication.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cdc6p and cdc18+ are essential, rate-limiting proteins for DNA replication initiation in yeast.
- These proteins also play roles in cell cycle checkpoint controls, ensuring DNA replication completion before mitosis.
Purpose of the Study:
- To identify and characterize proteins in Xenopus and humans homologous to yeast Cdc6p/cdc18.
- To investigate the structure, localization, and expression patterns of the human p62(cdc6) protein.
Main Methods:
- Sequence homology searches to identify related proteins.
- Bioinformatic analysis of human p62(cdc6) for functional domains.
- Analysis of p62(cdc6) mRNA and protein expression in human diploid fibroblasts during cell cycle progression.
Main Results:
- Homologous proteins to Cdc6p/cdc18 were identified in Xenopus and humans.
- Human p62(cdc6) possesses domains characteristic of cell cycle regulatory proteins, including kinase phosphorylation sites and a nucleotide-binding domain.
- p62(cdc6) expression is low in quiescent cells and increases upon serum stimulation, coinciding with cell cycle reentry and DNA replication.
Conclusions:
- The identification of conserved structural features suggests fundamental similarities in DNA replication initiation complexes across eukaryotes.
- Human p62(cdc6) is a cell cycle-regulated protein involved in the control of DNA replication.