Mordes DA, et al. (2008) Dpb11 activates the Mec1-Ddc2 complex. Proc Natl Acad Sci U S A 105(48):18730-4
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.
| Status: Published | Type: Journal Article | PubMed ID: 19028869 |
Topics addressed in this paper
Number of different genes curated to this paper: 4
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| DDC1 | DPB11 | LCD1 | MEC1 | |
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