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Human DNA polymerase iota (hPol iota) is a member of the Y family of DNA polymerases, which are involved in translesion synthesis (TLS) past fork-blocking lesions in DNA. Whether hPol iota contributes to lesion bypass in intact human cells has not been determined. We showed previously that cells from xeroderma pigmentosum patients not only have a very significantly higher than normal frequency of UV-induced mutations [Maher et al. (1976) Nature 261:593-595], but the kinds of mutations induced differ very significantly from those found in normal cells [Wang et al.(1993) Mol. Cell. Biol. 13:4276-4283; McGregor et al. (1999) Mol. Cell. Biol. 19:147-154]. Cells from such patients are now known to lack hPol eta, which readily inserts A opposite UV-induced thymine-thymine pyrimidine dimers. To test the hypothesis that hPol iota, which is closely related to hPol eta, is responsible for the high frequency and very unusual spectrum of mutations induced by UV in cells lacking hPol eta, we stably transfected such XP variant cells with antisense against hPol iota and determined the effect on expression of hPol iota protein and on the frequency and spectrum of mutations induced in the HPRT gene the results support our hypothesis. (Supported by NIH CA098305 to VMM and by 1Z01HD001500-21 to RW).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]