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The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η

Nature volume 399, pages 700–704 (1999)Cite this article

Abstract

Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers. Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA1,2. It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis, but the gene product has never been isolated. Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts3. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase η (ref. 4). This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins5,6,7,8,9,10 which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase η gene. Recombinant human DNA polymerase η corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together, these results indicate that DNA polymerase η could be the XPV gene product.

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Figure 1: Deduced amino-acid sequence of XPV protein.
Figure 2: Northern-blot analysis of XPV .
Figure 3: Mutations in the XPV cDNA of XP-V cells.
Figure 4: Activity of recombinant XPV protein.

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Acknowledgements

We thank members of F.H.'s laboratory for helpful discussions, K. Tanaka for XP2SA cells, and J. H. J. Hoeijmakers for XP7TA, XP1RO, XP30RO and XP4BE cells. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan, and from the Biodesign Research Program of the Institute of Physical and Chemical Research (RIKEN), M.Y. is a special postdoctoral researcher of RIKEN.

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Authors and Affiliations

  1. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, 565-0871, Osaka, Japan

    Chikahide Masutani, Rika Kusumoto, Ayumi Yamada, Masayuki Yokoi, Mayumi Yuasa, Marito Araki & Fumio Hanaoka

  2. Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, 630-01, Nara, Japan

    Rika Kusumoto

  3. Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamada-oka, Suita, 565-0871, Osaka, Japan

    Ayumi Yamada & Marito Araki

  4. Institute of Physical and Chemical Research (RIKEN), Wako-shi, 351-0198, Saitama, Japan

    Naoshi Dohmae, Masayuki Yokoi, Marito Araki, Koji Takio & Fumio Hanaoka

  5. Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, 565-0874, Osaka, Japan

    Shigenori Iwai

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  1. Chikahide Masutani
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Correspondence to Fumio Hanaoka.

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Masutani, C., Kusumoto, R., Yamada, A. et al. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η. Nature 399, 700–704 (1999). https://doi.org/10.1038/21447

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