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| Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta |
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| Author(s): Yamada A, Masutani C, Iwai S, Hanaoka F |
| Source: NUCLEIC ACIDS RESEARCH Volume: 28 Issue: 13 Pages: 2473-2480 Published: JUL 1 2000 |
| Times Cited: 54 References: 41 |
| Abstract: Defects in the human gene XPV result in the variant form of the genetic disease xeroderma pigmentosum (XP-V), XPV encodes DNA polymerase eta, 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 similar to 4-fold during cell proliferation. These results suggest that DNA polymerase eta plays a role in DNA replication, though the enzyme is not essential for viability. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hanaoka, F (reprint author), Osaka Univ, Inst Mol & Cellular Biol, 1-3 Yamada Oka, Suita, Osaka 5650871 Japan |
Addresses:
1. Osaka Univ, Inst Mol & Cellular Biol, Suita, Osaka 5650871 Japan
2. Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871 Japan
3. Japan Sci & Technol Corp, CREST, Suita, Osaka 5650871 Japan
4. RIKEN, Wako, Saitama 3510198 Japan
5. Biomol Engn Res Inst, Suita, Osaka 5650874 Japan |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 332JN |
| ISSN: 0305-1048 |
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