Moriya, Yang and Hashimoto

DNA polymerases play a central role in the replication and repair of DNA. Recently, a number of previously unknown DNA polymerases, including pol z, pol h, pol k, and pol i, were identified in human cells. In contrast to pol a and d, which negotiate DNA damage with difficulty, these "new" polymerases catalyze DNA synthesis efficiently, albeit with low fidelity, on damaged templates in vitro. Pol z is responsible for UV-induced mutagenesis. Pol h (XPV), a homolog of Rad30 in yeast, catalyzes error-free bypass of cis-syn pyrimidine dimmers while translesion synthesis across benzo(a)pyrene adducts by pol h is error-prone. Humans lacking pol h exhibit an XP-variant phenotype, which is manifested by hypersensitivity to UV light and increased incidence of skin cancer.

The presence of "translesion" DNA polymerases in eukaryotes raises many important questions. What function(s) do these enzymes play in human cells? Do they contribute to "spontaneous" mutagenesis? Do they work in concert with pol d, pol b, or other polymerases to effect translesion synthesis? We address these and related questions in this research.

• Liu, X., Lao, Y., Yang, I.Y, Hecht, SS and Moriya, M., Replication-coupled repair of crotonaldehyde/acetyladehyde-induced guanine-guanine interstrand cross-links and their mutagenicity Biochemistry, 45: 12898-905, 2006
• Pollack,M, Yang, IY, Kim, HY,Blair, IA and Moriya, M. Translesion DNA synthesis across the heptanone-etheno-2’-dexycytidine adduct in cells. Chem Res Toxicol 19: 1074-9, 2006
• Stein, S, Lao, Y, Yang, IY, Hecht, SS and Moriya, M., Genotoxicity of acetaldehyde and crotanaldehyde-induced 1, N2-propanodeoxyguanosine DNA adducts in human cells. Mutat Res. 608: 1-7, 2006
• Yang, I.-Y., Miller, H., Wang, Z., Frank, E., Ohmori, H., Hanaoka, F. and Moriya, M., Mammalian translesion DNA synthesis across an acrolein-drived deoxyguanosine adduct: participation of pol h in error-prone synthesis in human cells, J. Biol. Chem. 278, 13989-13994, 2003.
• Friedberg, E.C., and Gerlach, V.L., Novel DNA polymerases offer clues to the molecular basis of mutagenesis, Cell 98, 413-416, 1999

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