Role of specialized DNA polymerases in mutagenesis and DNA repair

Moriya and Hashimoto

Image: DNA PolymeraseDNA 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.

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