David Cortez
Faculty Member
Last active: 2/4/2016

Dpb11 activates the Mec1-Ddc2 complex.

Mordes DA, Nam EA, Cortez D
Proc Natl Acad Sci U S A. 2008 105 (48): 18730-4

PMID: 19028869 · PMCID: PMC2596233 · DOI:10.1073/pnas.0806621105

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.

MeSH Terms (13)

Adaptor Proteins, Signal Transducing Cell Cycle Proteins DNA Damage DNA Repair Enzyme Activation Humans Hydroxyurea Intracellular Signaling Peptides and Proteins Nucleic Acid Synthesis Inhibitors Phosphoproteins Protein-Serine-Threonine Kinases Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins

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