Journal
EMBO REPORTS
Volume 8, Issue 11, Pages 1074-1079Publisher
WILEY
DOI: 10.1038/sj.embor.7401084
Keywords
azathioprine; PCNA; reactive oxygen; skin cancer; thioguanine
Categories
Ask authors/readers for more resources
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 ( O-1(2)) when exposed to UVA. Here, we show that this O-1(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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available