Dpb11 activates the Mec1–Ddc2 complex | Zendy

Daniel A. Mordes | Zendy; Edward A. Nam | Zendy; David Cortez | Zendy

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Dpb11 activates the Mec1–Ddc2 complex

Author(s) -

Daniel A. Mordes,

Edward A. Nam,

David Cortez

Publication year - 2008

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0806621105

Subject(s) - regulator , biology , saccharomyces cerevisiae , kinase , g2 m dna damage checkpoint , microbiology and biotechnology , cell cycle checkpoint , genetics , gene , cell cycle

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.

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