Abstract
HUMANS with a defect in the XPG protein suffer from xeroderma pigmentosum (XP) resulting from an inability to perform DNA nucleotide excision repair properly1–4. Here we show that XPG makes a structure-specific endonucleolytic incision in a synthetic DNA substrate containing a duplex region and single-stranded arms. One strand of the duplex is cleaved at the border with single-stranded DNA. A cut with the same polarity is also made in a bubble structure, at the 3′ side of the centrally unpaired region. Normal cell extracts introduce a nick 3′ to a platinum – DNA lesion, but an XP-G cell extract is defective in making this incision. These data show that XPG has a direct role in making one of the incisions required to excise a damaged oligonucleotide, by cleaving 3' to DNA damage during nucleotide excision repair.
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References
Keijzer, W. et al. Mutat. Res. 62, 183–190 (1979).
Arlett, C. F. et al. Carcinogenesis 1, 745–751 (1980).
Ichihashi, M., Fujiwara, Y., Uehara, Y. & Matsumoto, A. J. invest. Dermatol. 85, 284–287 (1985).
Norris, P. G., Hawk, J. L. M., Avery, J. A. & Giannelli, F. Br. J. Dermatol. 116, 861–866 (1987).
O'Donovan, A., Scherly, D., Clarkson, S. G. & Wood, R. D. J. biol. Chem. 269, 15965–15968 (1994).
Habraken, Y., Sung, P., Prakash, L. & Prakash, S. Nature 366, 365–368 (1993).
Tomkinson, A. E., Bardwell, A. J., Bardwell, L., Tappe, N. J. & Friedberg, E. C. Nature 362, 860–862 (1993).
Sung, P., Reynolds, P., Prakash, L. & Prakash, S. J. biol. Chem. 268, 26391–26399 (1993).
Biggerstaff, M., Szymkowski, D. E. & Wood, R. D. EMBO J. 12, 3685–3692 (1993).
van Vuuren, A. J. et al. EMBO J. 12, 3693–3701 (1993).
Reardon, J. T., Thompson, L. H. & Sancar, A. Cold Spring Harb. Symp. quant. Biol. 58, 605–617 (1993).
Aboussekhra, A. & Wood, R. D. Curr. Opin. Genet. Dev. 4, 212–220 (1994).
O'Donovan, A. & Wood, R. D. Nature 363, 185–188 (1993).
Svoboda, D. L., Taylor, J. S., Hearst, J. E. & Sancar, A. J. biol. Chem. 268, 1931–1936 (1993).
Lin, J. J., Phillips, A. M., Hearst, J. E. & Sancar, A. J. biol. Chem. 267, 17693–17700 (1992).
Scherly, D. et al. Nature 363, 182–185 (1993).
Carr, A. M. et al. Nucleic Acids Res. 21, 1345–1349 (1993).
Maclnnes, M. A. et al. Molec. cell. Biol. 13, 6393–6402 (1993).
Shiomi, T. et al. Mutat. Res. 314, 167–175 (1994).
Harrington, J. J. & Lieber, M. R. Genes Dev. 8, 1344–1355 (1994).
Murray, J. M. et al. Molec. cell. Biol. 14, 4878–4888 (1994).
Vermeulen, W., Jaeken, J., Jaspers, N. G. J., Bootsma, D. & Hoeijmakers, J. H. J. Am. J. hum. Genet. 53, 185–192 (1993).
Bootsma, D. & Hoeijmakers, J. H. J. Nature 363, 114–115 (1993).
Bennett, R. J., Dunderdale, H. & West, S. Cell 74, 1021–1031 (1993).
Szymkowski, D. E., Yarema, K., Essigmann, J. E., Lippard, S. J. & Wood, R. D. Proc. natn. Acad. Sci. U.S.A. 89, 10772–10776 (1992).
Shivji, M. K. K., Kenny, M. K. & Wood, R. D. Cell 69, 367–374 (1992).
Bardwell, L. et al. Science (in the press).
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O'Donovan, A., Davies, A., Moggs, J. et al. XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair. Nature 371, 432–435 (1994). https://doi.org/10.1038/371432a0
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DOI: https://doi.org/10.1038/371432a0
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