1. Structural Basis for the Recognition of DNA Repair Proteins UNG2, XPA, and RAD52 by Replication Factor RPA
- Author
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Rajesh Gupta, Walter J. Chazin, Elena Bochkareva, Alexey Bochkarev, C. James Ingles, Aled M. Edwards, Georges Mer, and Lori Frappier
- Subjects
Models, Molecular ,Saccharomyces cerevisiae Proteins ,HMG-box ,DNA Repair ,DNA repair ,Macromolecular Substances ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Eukaryotic DNA replication ,Biology ,DNA polymerase delta ,General Biochemistry, Genetics and Molecular Biology ,Protein Structure, Secondary ,RNA Polymerase I ,Replication Protein A ,Humans ,Amino Acid Sequence ,Replication protein A ,Nuclear Magnetic Resonance, Biomolecular ,Genetics ,Binding Sites ,Biochemistry, Genetics and Molecular Biology(all) ,Helix-Loop-Helix Motifs ,Proteins ,RNA-Binding Proteins ,DNA ,Peptide Fragments ,Cell biology ,Protein Structure, Tertiary ,Xeroderma Pigmentosum Group A Protein ,DNA-Binding Proteins ,enzymes and coenzymes (carbohydrates) ,Origin recognition complex ,DNA mismatch repair ,Sequence Alignment ,Nucleotide excision repair ,Protein Binding - Abstract
Replication protein A (RPA), the nuclear ssDNA-binding protein in eukaryotes, is essential to DNA replication, recombination, and repair. We have shown that a globular domain at the C terminus of subunit RPA32 contains a specific 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 different repair pathway. NMR structures of the RPA32 domain, free and in complex with the minimal interaction domain of UNG2, were determined, defining a common structural basis for linking RPA to the nucleotide excision, base excision, and recombinational pathways of repairing damaged DNA. Our findings support a hand-off model for the assembly and coordination of different components of the DNA repair machinery.
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