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Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene

Oncogene volume 19, pages 4721–4728 (2000)Cite this article

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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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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Authors and Affiliations

  1. Institute for Molecular and Cellular Biology, Osaka University and CREST, Japan Science and Technology Corporation, 1-3 Yamada-Oka, Suita, Osaka, 565-0871, Japan

    Mayumi Yuasa, Chikahide Masutani & Fumio Hanaoka

  2. RIKEN (The Institute of Physical and Chemical Research), Wako-Shi, Saitama, 351-0198, Japan

    Toshihiko Eki & Fumio Hanaoka

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  1. Mayumi Yuasa
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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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