tailieunhanh - Báo cáo khoa học: Human Cdc45 is a proliferation-associated antigen

Cell division cycle protein 45 (Cdc45) plays a critical role in DNA replica-tion to ensure that chromosomal DNA is replicated only once per cell cycle. We analysed the expression of human Cdc45 in proliferating and nonproliferating cells. | ỊFEBS Journal Human Cdc45 is a proliferation-associated antigen S. Pollok1 C. Bauerschmidt2 J. Sanger3 . Nasheuer4 and F. Grosse1 5 1 Leibniz Institute for Age Research Fritz Lipmann Institute Jena Germany 2 Radiation Oncology and Biology University of Oxford UK 3 Institute of Pathology Bad Berka Germany 4 NationalUniversity of Ireland Department of Biochemistry Galway Ireland 5 Center for Molecular Biomedicine Friedrich Schiller University Jena Germany Keywords half life molecule number proliferation marker senescence terminal differentiation Correspondence F. Grosse Leibniz Institute for Age Research Fritz Lipmann Institute . Biochemistry Jena Germany Fax 49 3641-656288 Tel 49 3641 656290 E-mail fgrosse@ Received 9 March 2007 revised 21 May 2007 accepted 23 May 2007 doi Cell division cycle protein 45 Cdc45 plays a critical role in DNA replication to ensure that chromosomal DNA is replicated only once per cell cycle. We analysed the expression of human Cdc45 in proliferating and nonproliferating cells. Our findings show that Cdc45 protein is absent from long-term quiescent terminally differentiated and senescent human cells although it is present throughout the cell cycle of proliferating cells. Moreover Cdc45 is much less abundant than the minichromosome maintenance Mcm proteins in human cells supporting the concept that origin binding of Cdc45 is rate limiting for replication initiation. We also show that the Cdc45 protein level is consistently higher in human cancer-derived cells compared with primary human cells. Consequently tumour tissue is preferentially stained using Cdc45-specific antibodies. Thus Cdc45 expression is tightly associated with proliferating cell populations and Cdc45 seems to be a promising candidate for a novel proliferation marker in cancer cell biology. In an adult human body only a small proportion of cells actively progresses through the mitotic cell cycle in self-renewing tissues 1