Charting the landscape of tandem BRCT domain-mediated protein interactions.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Woods, NT; Mesquita, RD; Sweet, M; Carvalho, MA; Li, X; Liu, Y; Nguyen, H; Thomas, CE; Iversen, ES; Marsillac, S; Karchin, R; Koomen, J; Monteiro, ANA

Published Date

  • September 18, 2012

Published In

Volume / Issue

  • 5 / 242

Start / End Page

  • rs6 -

PubMed ID

  • 22990118

Pubmed Central ID

  • PMC4064718

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

International Standard Serial Number (ISSN)

  • 1945-0877

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2002255


  • eng