The Open UniversitySkip to content

Reactive oxygen-mediated damage to a human DNA replication and repair protein

Montaneri, Beatriz; O'Donovan, Peter; Reelfs, Olivier; Perrett, Conal M; Zhang, Xiaohong; Xu, Yao-Zhong; Ren, Xiaolin; Macpherson, Peter; Frith, David and Karran, Peter (2007). Reactive oxygen-mediated damage to a human DNA replication and repair protein. EMBO Reports, 8(11) pp. 1074–1079.

DOI (Digital Object Identifier) Link:
Google Scholar: Look up in Google Scholar


Ultraviolet A (UVA) makes up more than 90% of incident terrestrial ultraviolet radiation. Unlike shorter wavelength UVB, which damages DNA directly, UVA is absorbed poorly by DNA and is therefore considered to be less hazardous. Organ transplant patients treated with the immunosuppressant azathioprine frequently develop skin cancer. Their DNA contains 6-thioguanine-a base analogue that generates DNA-damaging singlet oxygen ((1)O(2)) when exposed to UVA. Here, we show that this (1)O(2) damages proliferating cell nuclear antigen (PCNA), the homotrimeric DNA polymerase sliding clamp. It causes covalent oxidative crosslinking between the PCNA subunits through a histidine residue in the intersubunit domain. Crosslinking also occurs after treatment with higher-although still moderate-doses of UVA alone or with chemical oxidants. Chronic accumulation of oxidized proteins is linked to neurodegenerative disorders and ageing. Our findings identify oxidative damage to an important DNA replication and repair protein as a previously unrecognized hazard of acute oxidative stress.

Item Type: Article
ISSN: 1469-3178
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 9903
Depositing User: Astrid Peterkin
Date Deposited: 23 Oct 2007
Last Modified: 04 Oct 2016 10:07
Share this page:


Scopus Citations

▼ Automated document suggestions from open access sources

Actions (login may be required)

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340