Inefficient bypass of an abasic site by DNA polymerase eta

DNA polymerase eta (Pol eta) bypasses a cis-syn thymine-thymine dimer effic iently and accurately, and inactivation of Pol eta in humans results in the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Also, Po l eta bypasses the 8-oxoguanine lesion efficiently by predominantly inserti ng a C opposite this lesion, and it bypasses the O-6-methylguanine lesion b y inserting a C or a T. To further assess the range of DNA lesions tolerate d by Pol eta, here we examine the bypass of an abasic site, a prototypical noninstructional lesion. Steady state kinetic analyses show that both yeast and human Pol eta are very inefficient in both inserting a nucleotide oppo site an abasic site and in extending from the nucleotide inserted. Hence, P ol eta bypasses this lesion extremely poorly. These results suggest that Po l eta requires the presence of template bases opposite both the incoming nu cleotide and the primer terminus to catalyze efficient nucleotide incorpora tion.