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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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DNA / chemistry
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DNA / metabolism
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DNA Repair
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Helix-Loop-Helix Motifs
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Humans
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Nuclear Magnetic Resonance, Biomolecular
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Peptide Fragments / chemistry*
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Peptide Fragments / metabolism*
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proteins / chemistry
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Proteins / metabolism
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RNA Polymerase I
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RNA-Binding Proteins / chemistry*
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RNA-Binding Proteins / metabolism*
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Recombinant Fusion Proteins
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Replication Protein A
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Xeroderma Pigmentosum Group A Protein
Substances
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DNA-Binding Proteins
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Macromolecular Substances
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Peptide Fragments
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Proteins
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RNA-Binding Proteins
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RPA1 protein, human
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RPA14 protein, S cerevisiae
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Recombinant Fusion Proteins
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Replication Protein A
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Saccharomyces cerevisiae Proteins
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XPA protein, human
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Xeroderma Pigmentosum Group A Protein
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DNA
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RNA Polymerase I