Structural Basis for Cell Cycle Checkpoint Control by the BRCA1-CtIP Complex.

摘要: The breast and ovarian tumor suppressor BRCA1 has important functions in cell cycle checkpoint control DNA repair. Two tandem C-terminal (BRCT) domains are essential for the suppression activity of interact a phosphorylation-dependent manner with proteins involved damage-induced control, including helicase BACH1 CtBP-interacting protein (CtIP). crystal structure BRCT repeats bound to PTRVSpSPVFGAT phosphopeptide corresponding residues 322−333 human CtIP was determined at 2.5 A resolution. peptide binds cleft formed by interface two BRCTs two-pronged manner, phospho-Ser327 Phe330 anchoring through extensive contacts residues. Several hydrogen bonds salt bridges that stabilize BRCA1−BACH1 complex missing BRCA1−CtIP interaction, offering structural basis ∼5-fold lower affinity compared BACH1, as ...