DNA polymerase η (Polη) bypasses a cis-syn thymine-thymine dimer efficiently and accurately, and inactivation of Polη in humans results in the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Also, Polη bypasses the 8-oxoguanine lesion efficiently by predominantly inserting a C opposite this lesion, and it bypasses the O 6-methylguanine lesion by inserting a C or a T. To further assess the range of DNA lesions tolerated by Polη, here we examine the bypass of an abasic site, a prototypical noninstructional lesion. Steady-state kinetic analyses show that both yeast and human Polη are very inefficient in both inserting a nucleotide opposite an abasic site and in extending from the nucleotide inserted. Hence, Polη bypasses this lesion extremely poorly. These results suggest that Polη requires the presence of template bases opposite both the incoming nucleotide and the primer terminus to catalyze efficient nucleotide incorporation.
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