TY - JOUR
T1 - Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA
AU - Mer, Georges
AU - Bochkarev, Alexey
AU - Gupta, Rajesh
AU - Bochkareva, Elena
AU - Frappier, Lori
AU - Ingles, C. James
AU - Edwards, Aled M.
AU - Chazin, Walter J.
N1 - Funding Information:
We thank C. Arrowsmith, D. Case, J. Tainer, M. V. Botuyan, J. Christodoulou, P. Fagan, S. Parikh, and S. Veeraraghavan for fruitful discussions; M. Pique for assistance with graphics; L. Mäler, J. Smith, and C. Weber for assistance with Amber; J. Chung for help in setup of NMR experiments; and M. V. Botuyan for protein purification. L. F. and A. M. E. are Medical Research Council of Canada Scientists. This research was supported by grants from the National Cancer Institute of Canada to C. J. I., L. F., and A. M. E., the National Institutes of Health to A. B., and the National Science Foundation (to W. J. C.). G. M. acknowledges the support of postdoctoral fellowships from the French Association for Cancer Research, the Philippe Foundation, Inc., and the Human Frontier Science Program Organization.
PY - 2000/10/27
Y1 - 2000/10/27
N2 - 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.
AB - 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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U2 - 10.1016/S0092-8674(00)00136-7
DO - 10.1016/S0092-8674(00)00136-7
M3 - Article
C2 - 11081631
AN - SCOPUS:0034721654
SN - 0092-8674
VL - 103
SP - 449
EP - 456
JO - Cell
JF - Cell
IS - 3
ER -