Structural basis for the recognition of DNA repair proteins UNG2, XPA, andRAD52 by replication factor RPA

Replication protein A (RPA), the nuclear ssDNA-binding protein in eukaryote s, is essential to DNA replication, recombination, and repair. We have show n that a globular domain at the C terminus of subunit RPA32 contains a spec ific surface that interacts in a similar manner with the DNA repair enzyme UNG2 and repair factors XPA and RAD52, each of which functions in a differe nt repair pathway. NMR structures of the RPA32 domain, free and in complex with the minimal interaction domain of UNG2, were determined, defining a co mmon structural basis for linking RPA to the nucleotide excision, base exci sion, and recombinational pathways of repairing damaged DNA. Our findings s upport a hand-off model for the assembly and coordination of different comp onents of the DNA repair machinery.