Mammalian Homologs of Yeast Checkpoint Genes
Abstract
We originally hypothesized that components of DNA-related checkpoint pathways in addition to members of the ATM protein/lipid kinase family are conserved in all eukaryotes. This was based on functional similarities in the pathways and the conservation between the evolutionarily disparate budding and fission yeasts 1. Our goal was to identify additional regulators of mammalian DNA checkpoints by virtue of structural and functional homology with known checkpoint genes in budding yeast. We had proposed to use both structural and functional screens to identify human homologs of yeast damage checkpoint proteins Rad53 and Rad9. Once identified, such components would be ordered into pathways for mammalian checkpoint function, with emphasis on p53 regulation, cell cycle regulation, and complementation of ATM defects. Experimental work over the past few years has completely confirmed this hypothesis, and led to major advances in understanding mammalian checkpoint systems. Our work was to identify a hypothetical mammalian homolog of Rad53 (Technical Objectives 1,2,3), and, when the homolog Chk2 was identified, to elucidate regulation of mammalian Rad53 (Chk2/Cds 1), and regulation of its targets (Technical Objective 4).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADB285707
Entities
People
- David F. Stern
Organizations
- Yale University