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Sci. Signal., 18 September 2012
Vol. 5, Issue 242, p. rs6
[DOI: 10.1126/scisignal.2002255]

RESEARCH RESOURCES

Charting the Landscape of Tandem BRCT Domain–Mediated Protein Interactions

Nicholas T. Woods1, Rafael D. Mesquita2*, Michael Sweet1,3, Marcelo A. Carvalho2,4, Xueli Li1, Yun Liu5, Huey Nguyen1, C. Eric Thomas6, Edwin S. Iversen Jr.7, Sylvia Marsillac1, Rachel Karchin5, John Koomen6, and Alvaro N. A. Monteiro1{dagger}

1 Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
2 Instituto Federal de Educação, Ciência e Tecnologia, Rio de Janeiro, RJ 20270, Brazil.
3 Graduate Program in Biomedical Sciences, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
4 Instituto Nacional do Câncer, Rio de Janeiro, RJ 20231, Brazil.
5 Institute for Computational Medicine, Department of Biochemical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
6 Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
7 Department of Statistical Science, Duke University, Durham, NC 27708, USA.

* Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941, Brazil.

Abstract: Eukaryotic cells have evolved an intricate system to resolve DNA damage to prevent its transmission to daughter cells. This system, collectively known as the DNA damage response (DDR) network, includes many proteins that detect DNA damage, promote repair, and coordinate progression through the cell cycle. Because defects in this network can lead to cancer, this network constitutes a barrier against tumorigenesis. The modular BRCA1 carboxyl-terminal (BRCT) domain is frequently present in proteins involved in the DDR, can exist either as an individual domain or as tandem domains (tBRCT), and can bind phosphorylated peptides. We performed a systematic analysis of protein-protein interactions involving tBRCT in the DDR by combining literature curation, yeast two-hybrid screens, and tandem affinity purification coupled to mass spectrometry. We identified 23 proteins containing conserved BRCT domains and generated a human protein-protein interaction network for seven proteins with tBRCT. This study also revealed previously unknown components in DNA damage signaling, such as COMMD1 and the target of rapamycin complex mTORC2. Additionally, integration of tBRCT domain interactions with DDR phosphoprotein studies and analysis of kinase-substrate interactions revealed signaling subnetworks that may aid in understanding the involvement of tBRCT in disease and DNA repair.

{dagger} To whom correspondence should be addressed. E-mail: alvaro.monteiro{at}moffitt.org

Citation: N. T. Woods, R. D. Mesquita, M. Sweet, M. A. Carvalho, X. Li, Y. Liu, H. Nguyen, C. E. Thomas, E. S. Iversen, Jr., S. Marsillac, R. Karchin, J. Koomen, A. N. A. Monteiro, Charting the Landscape of Tandem BRCT Domain–Mediated Protein Interactions. Sci. Signal. 5, rs6 (2012).

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