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Science 9 July 1999:
Vol. 285. no. 5425, pp. 263 - 265
DOI: 10.1126/science.285.5425.263

Reports

hRAD30 Mutations in the Variant Form of Xeroderma Pigmentosum

Robert E. Johnson, Christine M. Kondratick, Satya Prakash, Louise Prakash *

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers.

Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6.104 Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555-1061, USA.
*   To whom correspondence should be addressed. E-mail: lprakash{at}scms.utmb.edu


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PNAS 99, 15548-15553
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The Role of Polymerase {eta} in Somatic Hypermutation Determined by Analysis of Mutations in a Patient with Xeroderma Pigmentosum Variant.
S. Yavuz, A. S. Yavuz, K. H. Kraemer, and P. E. Lipsky (2002)
J. Immunol. 169, 3825-3830
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Translesion DNA synthesis in eukaryotes: A one- or two-polymerase affair.
S. Prakash and L. Prakash (2002)
Genes & Dev. 16, 1872-1883
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DNA damage responses protect xeroderma pigmentosum variant from UVC-induced clastogenesis.
M. Cordeiro-Stone, A. Frank, M. Bryant, I. Oguejiofor, S. B. Hatch, L. D. McDaniel, and W. K. Kaufmann (2002)
Carcinogenesis 23, 959-966
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Low Fidelity DNA Synthesis by a Y Family DNA Polymerase Due to Misalignment in the Active Site.
R. J. Kokoska, K. Bebenek, F. Boudsocq, R. Woodgate, and T. A. Kunkel (2002)
J. Biol. Chem. 277, 19633-19638
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Human DNA polymerase mu (Pol {micro}) exhibits an unusual replication slippage ability at AAF lesion.
J.-B. Duvauchelle, L. Blanco, R. P. P. Fuchs, and A. M. Cordonnier (2002)
Nucleic Acids Res. 30, 2061-2067
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Posttranslational modification of the umuD-encoded subunit of Escherichia coli DNA polymerase V regulates its interactions with the beta processivity clamp.
M. D. Sutton, I. Narumi, and G. C. Walker (2002)
PNAS 99, 5307-5312
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Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion.
Y. Zhang, X. Wu, O. Rechkoblit, N. E. Geacintov, J.-S. Taylor, and Z. Wang (2002)
Nucleic Acids Res. 30, 1630-1638
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Preferential Misincorporation of Purine Nucleotides by Human DNA Polymerase eta Opposite Benzo[a]pyrene 7,8-Diol 9,10-Epoxide Deoxyguanosine Adducts.
D. Chiapperino, H. Kroth, I. H. Kramarczuk, J. M. Sayer, C. Masutani, F. Hanaoka, D. M. Jerina, and A. M. Cheh (2002)
J. Biol. Chem. 277, 11765-11771
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Quantitative measurement of translesion replication in human cells: Evidence for bypass of abasic sites by a replicative DNA polymerase.
S. Avkin, S. Adar, G. Blander, and Z. Livneh (2002)
PNAS 99, 3764-3769
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UV-induced T->C transition at a TT photoproduct site is dependent on Saccharomyces cerevisiae polymerase {eta}in vivo.
H. Zhang and W. Siede (2002)
Nucleic Acids Res. 30, 1262-1267
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Stimulation of DNA Synthesis Activity of Human DNA Polymerase {kappa} by PCNA.
L. Haracska, I. Unk, R. E. Johnson, B. B. Phillips, J. Hurwitz, L. Prakash, and S. Prakash (2002)
Mol. Cell. Biol. 22, 784-791
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Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.
B. C. Broughton, A. Cordonnier, W. J. Kleijer, N. G. J. Jaspers, H. Fawcett, A. Raams, V. H. Garritsen, A. Stary, M.-F. Avril, F. Boudsocq, et al. (2002)
PNAS
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