MAMMALIAN CELL CYCLE CHECKPOINT GENES

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DESCRIPTION: Cell cycle checkpoints arrest the cell division cycle at specific stages so DNA repair pathways can restore the integrity of the genome. Defects in checkpoint pathways can cause genomic instability and lead to cancer. A human cDNA, called hsrad17, has been cloned as the human homologue of fission yeast rad17, an essential component of the yeast S. pombe DNA damage/replication block checkpoint pathway. The objective of this proposal is to characterize hsrad17 in terms of its checkpoint function in mammalian cells, as well as its possible role as a tumor suppressor. Antisense technology and the introduction of antibodies will be used to deplete hsrad17 protein, and its role in checkpoint control will be tested. The hsrad17 locus will be mapped to a human chromosome. LOH and possible hsrad17 mutations in cancer will be investigated. Genetic screens will be used to isolate proteins that interact with the hsrad17 gene product to determine its function and the cell cycle pathways in which it is involved.