Interaction of replication protein A with two acidic peptides from human Bloom syndrome protein

Abstract

Bloom syndrome protein (BLM) is one of five human RecQ helicases which maintain genomic stability. Interaction of BLM with replication protein A (RPA) stimulates the DNA unwinding ability of BLM. The interaction is expected to be crucial in the DNA damage response. Although this stimulation of BLM by RPA is of particular importance in cancer cells, the precise binding surfaces of both proteins are not well understood. In this study, we show by fluorescence polarisation anisotropy that both acidic surface peptides of BLM specifically bind to the RPA70N domain of RPA. Our NMR analysis and docking models show that the basic cleft region of RPA70N is the binding site for both peptides and that the acidic peptide/basic cleft interaction governs RPA-BLM binding.