Dpb11 activates the Mec1-Ddc2 complex.
basic_science · Level V
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- Record sourced from PubMed, PMID 19028869.
- Also identified by DOI 10.1073/pnas.0806621105 and PMC identifier 2596233.
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Abstract
The Saccharomyces cerevisiae Mec1-Ddc2 checkpoint kinase complex (the ortholog to human ATR-ATRIP) is an essential regulator of genomic integrity. The S. cerevisiae BRCT repeat protein Dpb11 functions in the initiation of both DNA replication and cell cycle checkpoints. Here, we report a genetic and physical interaction between Dpb11 and Mec1-Ddc2. A C-terminal domain of Dpb11 is sufficient to associate with Mec1-Ddc2 and strongly stimulates the kinase activity of Mec1 in a Ddc2-dependent manner. Furthermore, Mec1 phosphorylates Dpb11 and thereby amplifies the stimulating effect of Dpb11 on Mec1-Ddc2 kinase activity. Thus, Dpb11 is a functional ortholog of human TopBP1, and the Mec1/ATR activation mechanism is conserved from yeast to humans.
Medical subject headings
- Cell Cycle Proteins
- Phosphoproteins
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins