Dpb11 activates the Mec1-Ddc2 complex
Open accessAbstract
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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In S. cerevisiae, Mec1 can be activated by Ddc1 and by Dpb11 recruited through Ddc1.
“In S. cerevisiae the Mec1 apical kinase can be activated both by the Ddc1 subunit of the checkpoint clamp and by the adaptor protein Dpb11 which is recruited at the lesion through interaction with Ddc1 [19–23].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [23]
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References 31 · Cited by 121
- Authors
- Mordes, D. A., Nam, E. A., & Cortez, D.
- Affiliations
- Vanderbilt University (US)
- Harvard University (US)
- Corresponding author
- Cortez, David
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-12-02
- Volume
- 105
- Issue
- 48
- Pages
- 18730-18734
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2596233
- OpenAlex
- W2015174686
- Cited by
- 121
- References
- 31
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 12 · 2012: 9
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Vanderbilt University
- National Cancer Institute (R01CA102729)
- National Institute of General Medical Sciences (T32-GM 07347, T32GM007347)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Dpb11, BRCT domain, DNA replication initiation, DNA damage checkpoint, kinase activation, Saccharomyces cerevisiae, genome stability
- MeSH terms
- DNA Damage, DNA Repair, Enzyme Activation, Humans, Hydroxyurea, Phosphoproteins, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Nucleic Acid Synthesis Inhibitors, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing
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