Abstract
The xeroderma pigmentosum variant (XP-V) is one of the most common forms of this cancer-prone syndrome. XP groups A through G are characterized by defective nucleotide excision repair, whereas the XP-V phenotype is proficient in this pathway. The XPV gene encodes DNA polymerase η, which catalyzes an accurate translesion synthesis, indicating that the XPV gene contributes tumor suppression in normal individuals. Here we describe the genomic structure and chromosomal localization of the XPV gene, which includes 11 exons covering the entire coding sequence, lacks a TATA sequence in the upstream region of the transcription-initiation, and is located at the chromosome band 6p21.1-6p12. Analyses of patient-derived XP-V cell lines strongly suggested that three of four cell lines carried homozygous mutations in the XPV gene. The fourth cell line, XP1RO, carried heterozygous point mutations in the XPV gene, one of which was located at the splice acceptor site of exon 2, resulting in the omission of exon 2 from the mature mRNA. These findings provide a basis for diagnosis and therapy of XP-V patients.
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References
Bray-Ward P, Menninger J, Lieman J, Desai T, Mokady N, Banks A and Ward DC. . 1996 Genomics 32: 1–14.
Carty MP, Lawrence CW and Dixon K. . 1996 J. Biol. Chem. 271: 9637–9647.
Cleaver JE. . (1972). J. Invest. Dermatol. 58: 124–128.
Cordeiro-Stone M, Zaritskaya LS, Price LK and Kaufmann WK. . 1997 J. Biol. Chem. 272: 13945–13954.
Cordonnier AM, Lehmann AR and Fuchs RPP. . 1999 Mol. Cell. Biol. 19: 2206–2211.
Ensch-Simon I, Burgers PMJ and Taylor J-S. . (1998). Biochemistry 37: 8218–8226.
Friedberg EC, Walker GC and Siede W. . 1995 DNA Repair and Mutagenesis. ASM Press: Washington, DC.
Gerlach VL, Aravind L, Gotway G, Schultz RA, Koonin EV and Friedberg EC. . 1999 Proc. Natl. Acad. Sci. USA 96: 11922–11927.
Gibbs PEM, McGregor WG, Maher VM, Nisson P and Lawrence CW. . 1998 Proc. Natl. Acad. Sci. USA 95: 6876–6880.
Gibbs PEM, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW and Maher VM. . 2000 Proc. Natl. Acad. Sci. USA 97: 4186–4191.
Helin K. . 1998 Curr. Opin. Genet. Dev. 8: 28–35.
Javahery R, Khachi A, Lo K, Zenzie-Gregory B and Smale ST. . 1994 Mol. Cell. Biol. 14: 116–127.
Johnson RE, Kondratick CM, Prakash S and Prakash L. . 1999 Science 285: 263–265.
Johnson RE, Prakash S and Prakash L. . 2000 Proc. Natl. Acad. Sci. USA 97: 3838–3843.
Jones NC, Rigby PWJ and Ziff EB. . 1988 Genes Dev. 2: 267–281.
Lehmann AR, Kirk-Bell S, Arlett CF, Paterson MC, Lohman PHM, de Weerd-Kastelein EA and Bootsma D. . 1975 Proc. Natl. Acad. Sci. USA 72: 219–223.
Lim, S-K and Maquat LE. . 1992 EMBO J. 11: 3271–3278.
Lin W, Wu X and Wang Z. . 1999a). Mutat. Res. 433: 89–98.
Lin W, Xin H, Zhang Y, Wu X, Yuan F and Wang Z. . 1999b Nucleic Acids Res. 27: 4468–4475.
Maher VM, Ouellette LM, Curren RD and McCormick JJ. . 1976 Nature 261: 593–595.
Masutani C, Araki M, Yamada A, Kusumoto R, Nogimori T, Maekawa T, Iwai S and Hanaoka F. . 1999a EMBO J. 18: 3491–3501.
Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K and Hanaoka F. . 1999b Nature 399: 700–704.
Matsuda T, Bebenek K, Masutani C, Hanaoka F and Kunkel TA. . 2000 Nature 404: 1011–1013.
McDonald JP, Rapicć-Otrin V, Epstein JA, Broughton BC, Wang X, Lehmann AR, Wolgemuth DJ and Woodgate R. . 1999 Genomics 60: 20–30.
Misra RR and Vos J-MH. . 1993 Mol. Cell. Biol. 13: 1002–1012.
Mitchell PJ and Tjian R. . 1989 Science 245: 371–378.
Mitelman F, Mertens F and Johansson B. . 1997 Nature Genet. 15: 417–474.
Muhlrad D and Parker R. . 1994 Nature 370: 578–581.
Ogi T, Kato T-J, Kato T and Ohmori H. . 1999 Genes Cells 4: 607–618.
Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan Z-Q, Hurwitz J, Shiratori A, Murakami Y, Ozawa K and Eki T. . 1995 Genomics 25: 274–278.
Smale ST. . 1997 Biochim. Biophys. Acta 1351: 73–88.
Svoboda DL, Briley LP and Vos J-MH. . 1998 Cancer Res. 58: 2445–2448.
Takahashi E, Hori T, O'Connell P, Leppert M and White R. . 1990 Hum. Genet. 86: 14–16.
Wang YC, Maher VM, Mitchell DL and McCormick JJ. . 1993 Mol. Cell. Biol. 13: 4276–4283.
Wang YC, Maher VM and McCormick JJ. . 1991 Proc. Natl. Acad. Sci. USA 88: 7810–7814.
Waters HL, Seetharam S, Seidman MM and Kraemer KH. . 1993 J. Invest. Dermatol. 101: 744–748.
Weis L and Reinberg D. . 1992 FASEB J. 6.: 3300–3309.
Xiao W, Lechler T, Chow BL, Fontanie T, Agustus M, Carter KC and Wei Y-F. . 1998 Carcinogenesis 19: 945–949.
Yamada A, Masutani C, Iwai S and Hanaoka F. . 2000 Nucleic Acids Res. 28: 2473–2480.
Zenzie-Gregory B, O'Shea-Greenfield A and Smale ST. . 1992 J. Biol. Chem. 267: 2823–2830.
Acknowledgements
We are grateful to Dr Yoshiaki Ohkuma, Dr Masayuki Yokoi, Dr Marito Araki, Ayumi Yamada, Rika Kusumoto, Tomokazu Nogimori and other members of Dr Hanaoka's laboratory at Osaka University for helpful suggestions and discussions. We thank Dr Katsuzumi Okumura (Mie University) for helpful comments on FISH analysis. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan, from the Core Research for Evolutional Science and Technology (CREST), and from the Biodesign Research Program of RIKEN.
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Yuasa, M., Masutani, C., Eki, T. et al. Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene. Oncogene 19, 4721–4728 (2000). https://doi.org/10.1038/sj.onc.1203842
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DOI: https://doi.org/10.1038/sj.onc.1203842
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