Protein-protein interactions mediated by the carboxy terminus domains of breast cancer gene 1 (BRCT) play a critical role in the regulation of cell cycle checkpoints in response to DNA damage. DNA damage-induced checkpoint regulation bestows radiation resistance to cancers, and inhibition of the proteins involved has been suggested as potential drug targets. Structural studies show that BRCT binding peptides, namely BACH1 and CUP that are important for cell cycle regulation, occupy the exact same site on BRCT through a pSXXF consensus recognition sequence. In the present study we use two complementary techniques, isothermal titration calorimetry (ITC) and fluorescence polarization (FP), to define structural minima of a BACH1 peptide. Remarkably the minimal tetrapeptide retains low-micromolar affinity for BRCT with a thermodynamic signature comparable to the decapeptide. The study also identifies a potential hydrophobic pocket adjacent to the pSXXF motif and intramolecular hydrogen bonds that can be exploited during inhibitor design.