Sunday, October 16, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP082) Novel UVB-induced mitochondrial deletions in human epithelial cells.

Steinberg, Mark*,1, Hill, Helene2, Pierre, Zdenka 1, Liu, Suqing 1, Hwang, Bor-Jang 1, Ji, Fang1, Hubbard, Karen3, Dermody, James4, 1 Department of Chemistry, New York, NY, US2 Department of Radiology, Newark, NJ, US3 Department of Biology, New York, NY, US4 Department of Microbiology and Molecular Genetics, Newark, NJ

ABSTRACT- We examined mitochondrial deletions in a line of human epithelial cells following a single irradiation of 228 J/M2 from an FS20 UVB light source. We observed at least 2 distinct Mt deletions: 1. the widely observed 4977 bp common deletion (CD) and 2. a novel 5128 bp deletion flanked by TAGG repeats at nt 8247-8250 and 13375-13378 that has not, to our knowledge been previously described. Although the novel deletion was strongly induced in the irradiated cells, we found it to be widely and variably distributed in a variety of cells examined including specimens of intact skin and cultured human fibroblasts. Since the terminal tetrameric sequences are inverted complements of one another rather than direct repeats, the mechanism of deletion would appear to require alignment of the tetramers in parallel possibly involving a triple helical intermediate or a distorted duplex stabilized by Hoogsteen base pairs. This deletion is detected using a forward primer that spans the deletion junction.

Key words: UV-induced mitochondrial DNA damage, mitochondrial deletions, reactive oxygen species damage, environmental radiation effects

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2005 RRS