Tandem BRCT Domains: DNA's Praetorian Guard

Abstract

The cell’s ability to sense and respond to specific stimuli is a complex system derived from precisely regulated protein-protein interactions. Some of these protein-protein interactions are mediated by the recognition of linear peptide motifs by protein modular domains. BRCT (BRCA1 C-terminal) domains and their linear motif counterparts, which contain phosphoserines, are one such pair-wise interaction system that seems to have evolved to serve as a surveillance system to monitor threats to the cell’s genetic integrity. Evidence indicates that BRCT domains found in tandem can cooperate to provide sequence specific binding of phosphorylated peptides as is the case for the breast and ovarian cancer susceptibility gene BRCA1 and the PAX transcription factor interacting protein PAXIP1. Particular interest has been paid to tandem BRCT domains as ‘readers’ of signaling events in the form of phosphorylated serine moieties induced by the activation of DNA damage response kinases ATM, ATR and DNA-PK. However, given the diversity of tandem BRCT containing proteins questions remain as to the origin and evolution of this domain. Here we discuss emerging views of the origin and evolving roles of tandem BRCT domain repeats in the DNA damage response.

Long-chain acyl-CoA synthetase 2 knockdown leads to decreased fatty acid oxidation in fat body and reduced reproductive capacity in the insect Rhodnius prolixus

“…Genes were searched in the R. prolixus genome assembly (VectorBase, http://www.vectorbase.org, R. prolixus CDC annotation, RproC1) [22] by similarity to the AMP-binding family consensus sequence (Pfam number PF00501) using FAT software [23]. Retrieved sequences were manually analyzed to confirm the presence of additional ACS conserved motifs [24, 25].…”

Charting the Landscape of Tandem BRCT Domain–Mediated Protein Interactions

“…BRCT domains are present in a large superfamily of ~40 nonorthologous proteins that participate in cell cycle checkpoints and in the DDR (14, 15). BRCT domains are versatile modules that mediate protein-protein and protein-nucleic acid interactions (16). Several BRCT domains recognize linear motifs phosphorylated by kinases that are activated by DNA damage (8, 9, 17).…”

The Ect2 Rho Guanine Nucleotide Exchange Factor Is Essential for Early Mouse Development and Normal Cell Cytokinesis and Migration

“…For example, among all human RhoGEFs, only Ect2 contains tandem BRCT (BRCA1 Cterminal) domains that are normally found in proteins (e.g., BRCA1, TP53BP1) involved in DNA damage signaling, repair, and coordination of cell cycle checkpoints. 7,8 The BRCT domains may serve to regulate the RhoGEF catalytic activity and additionally can interact with phosphorylated proteins that dictate Ect2 subcellular localization. [9][10][11] Ect2 is also only one of 2 Dbl family RhoGEFs, aside from Net1, 12 that exhibits a nuclear localization in interphase cells.…”