Nucleic Acids Research, 2000, Vol. 28, No. 13 2473-2480
© 2000 Oxford University Press
Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase 
1Institute for Molecular and Cellular Biology, Osaka University and CREST, Japan Science and Technology Corporation, 1-3 Yamada-oka and 2The Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan, 3Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan and 4RIKEN, Wako, Saitama 351-0198, Japan
Defects in the human gene XPV result in the variant form of the genetic disease xeroderma pigmentosum (XP-V). XPV encodes DNA polymerase 
, a novel DNA polymerase that belongs to the UmuC/DinB/Rad30 superfamily. This polymerase catalyzes the efficient and accurate translesion synthesis of DNA past cis-syn cyclobutane di-thymine lesions. In this report we present the cDNA sequence and expression profiles of the mouse XPV gene and demonstrate its ability to complement defective DNA synthesis in XP-V cells. The mouse XPV protein shares 80.3% amino acid identity and 86.9% similarity with the human XPV protein. The recombinant mouse XPV protein corrected the inability of XP-V cell extracts to carry out DNA replication, by bypassing thymine dimers on template DNA. Transfection of the mouse or human XPV cDNA into human XP-V cells corrected UV sensitivity. Northern blot analysis revealed that the mouse XPV gene is expressed ubiquitously, but at a higher level in testis, liver, skin and thymus compared to other tissues. Although the mouse XPV gene was not induced by UV irradiation, its expression was elevated ~4-fold during cell proliferation. These results suggest that DNA polymerase plays a role in DNA replication, though the enzyme is not essential for viability.
* To whom correspondence should be addressed at: Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel: +81 6 6879 7975; Fax: +81 6 6877 9382; Email: fhanaoka@imcb.osaka-u.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. S. Waters, B. K. Minesinger, M. E. Wiltrout, S. D'Souza, R. V. Woodruff, and G. C. Walker Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance Microbiol. Mol. Biol. Rev., March 1, 2009; 73(1): 134 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ukai, K. Ishimaru, R. Ouchida, H. Mori, C. Kano, T. Moritan, and J.-Y. Wang Induction of A:T Mutations Is Dependent on Cellular Environment but Independent of Mutation Frequency and Target Gene Location J. Immunol., December 1, 2008; 181(11): 7835 - 7842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shiomi, C. Masutani, F. Hanaoka, H. Kimura, and T. Tsurimoto A Second Proliferating Cell Nuclear Antigen Loader Complex, Ctf18-Replication Factor C, Stimulates DNA Polymerase {eta} Activity J. Biol. Chem., July 20, 2007; 282(29): 20906 - 20914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ohkumo, Y. Kondo, M. Yokoi, T. Tsukamoto, A. Yamada, T. Sugimoto, R. Kanao, Y. Higashi, H. Kondoh, M. Tatematsu, et al. UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase {eta} and Mesenchymal Tumors in Mice Deficient for DNA Polymerase {iota} Mol. Cell. Biol., October 15, 2006; 26(20): 7696 - 7706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Lin, A. B. Clark, S. D. McCulloch, T. Yuan, R. T. Bronson, T. A. Kunkel, and R. Kucherlapati Increased Susceptibility to UV-Induced Skin Carcinogenesis in Polymerase {eta}-deficient Mice Cancer Res., January 1, 2006; 66(1): 87 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kusumoto, C. Masutani, S. Shimmyo, S. Iwai, and F. Hanaoka DNA binding properties of human DNA polymerase {eta}: implications for fidelity and polymerase switching of translesion synthesis Genes Cells, December 1, 2004; 9(12): 1139 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Johansson, A. Lagerqvist, K. Erixon, and D. Jenssen A method to monitor replication fork progression in mammalian cells: nucleotide excision repair enhances and homologous recombination delays elongation along damaged DNA Nucleic Acids Res., November 10, 2004; 32(20): e157 - e157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, Z. Chen, Y. Liu, R. J. Hickey, and L. H. Malkas Altered DNA Polymerase {iota} Expression in Breast Cancer Cells Leads to a Reduction in DNA Replication Fidelity and a Higher Rate of Mutagenesis Cancer Res., August 15, 2004; 64(16): 5597 - 5607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. McDonald, E. G. Frank, B. S. Plosky, I. B. Rogozin, C. Masutani, F. Hanaoka, R. Woodgate, and P. J. Gearhart 129-derived Strains of Mice Are Deficient in DNA Polymerase {iota} and Have Normal Immunoglobulin Hypermutation J. Exp. Med., August 18, 2003; 198(4): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Stary, P. Kannouche, A. R. Lehmann, and A. Sarasin Role of DNA Polymerase {eta} in the UV Mutation Spectrum in Human Cells J. Biol. Chem., May 23, 2003; 278(21): 18767 - 18775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.-Y. Yang, H. Miller, Z. Wang, E. G. Frank, H. Ohmori, F. Hanaoka, and M. Moriya Mammalian Translesion DNA Synthesis across an Acrolein-derived Deoxyguanosine Adduct. PARTICIPATION OF DNA POLYMERASE eta IN ERROR-PRONE SYNTHESIS IN HUMAN CELLS J. Biol. Chem., April 11, 2003; 278(16): 13989 - 13994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. I. Pavlov, I. B. Rogozin, A. P. Galkin, A. Y. Aksenova, F. Hanaoka, C. Rada, and T. A. Kunkel Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene PNAS, July 23, 2002; 99(15): 9954 - 9959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. MASUTANI, R. KUSUMOTO, A. YAMADA, M. YUASA, M. ARAKI, T. NOGIMORI, M. YOKOI, T. EKI, S. IWAI, and F. HANAOKA Xeroderma Pigmentosum Variant: From a Human Genetic Disorder to a Novel DNA Polymerase Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 71 - 80. [Abstract] [PDF]
|
|
|
|
|
|
Y. Murakumo, Y. Ogura, H. Ishii, S.-i. Numata, M. Ichihara, C. M. Croce, R. Fishel, and M. Takahashi Interactions in the Error-prone Postreplication Repair Proteins hREV1, hREV3, and hREV7 J. Biol. Chem., September 14, 2001; 276(38): 35644 - 35651. [Abstract] [Full Text] [PDF]
|
|