RRC ID 41361
Author Oikawa S, Tada-Oikawa S, Kawanishi S.
Title Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening.
Journal Biochemistry
Abstract Telomere shortening is associated with cellular senescence. We investigated whether UVA, which contributes to photoaging, accelerates telomere shortening in human cultured cells. The terminal restriction fragment (TRF) from WI-38 fibroblasts irradiated with UVA (365-nm light) decreased with increasing irradiation dose. Furthermore, UVA irradiation dose-dependently increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in both WI-38 fibroblasts and HL-60 cells. To clarify the mechanism of the acceleration of telomere shortening, we investigated site-specific DNA damage induced by UVA irradiation in the presence of endogenous photosensitizers using (32)P 5'-end-labeled DNA fragments containing the telomeric oligonucleotide (TTAGGG)(4). UVA irradiation with riboflavin induced 8-oxodG formation in the DNA fragments containing telomeric sequence, and Fpg protein treatment led to chain cleavages at the central guanine of 5'-GGG-3' in telomere sequence. The amount of 8-oxodG formation in DNA fragment containing telomere sequence [5'-CGC(TTAGGG)(7)CGC-3'] was approximately 5 times more than that in DNA fragment containing nontelomere sequence [5'-CGC(TGTGAG)(7)CGC-3']. Catalase did not inhibit this oxidative DNA damage, indicating no or little participation of H(2)O(2) in DNA damage. These results indicate that the photoexcited endogenous photosensitizer specifically oxidizes the central guanine of 5'-GGG-3' in telomere sequence to produce 8-oxodG probably through an electron-transfer reaction. It is concluded that the site-specific damage in telomere sequence induced by UVA irradiation may participate in the increase of telomere shortening rate.
Volume 40(15)
Pages 4763-8
Published 2001-4-17
DOI 10.1021/bi002721g
PII bi002721g
PMID 11294644
MeSH Base Sequence / radiation effects Cell Line Chromatography, High Pressure Liquid DNA Damage* DNA-Formamidopyrimidine Glycosylase Deoxyguanosine / analogs & derivatives* Deoxyguanosine / biosynthesis Deoxyguanosine / radiation effects Electrochemistry Fibroblasts / physiology Fibroblasts / radiation effects Guanine / radiation effects* HL-60 Cells Humans Light N-Glycosyl Hydrolases / physiology Photosensitizing Agents / pharmacology Riboflavin / physiology Telomere / genetics* Telomere / metabolism Telomere / radiation effects* Ultraviolet Rays*
IF 2.952
Times Cited 100
Human and Animal Cells