Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA.
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.
Mer
G
G
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Bochkarev
A
A
Gupta
R
R
Bochkareva
E
E
Frappier
L
L
Ingles
C J
CJ
Edwards
A M
AM
Chazin
W J
WJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012318:RNA Polymerase I; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011506:Proteins; D016601:RNA-Binding Proteins; C497167:RPA1 protein, human; C093847:RPA14 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D004247:DNA; D012318:RNA Polymerase I