DNA polymerase θ (Pol θ) is implicated in various cellular processes including 
double-strand break repair and apurinic/apyrimidinic site bypass. Because Pol θ 
expression correlates with poor cancer prognosis, the ability of Pol θ to bypass 
the C4'-oxidized abasic site (C4-AP) and 2-deoxyribonolactone (L), which are 
generated by cytotoxic agents, is of interest. Translesion synthesis and 
subsequent extension by Pol θ past C4-AP or L and an abasic site (AP) or its 
tetrahydrofuran analogue (F) was examined. Pol θ conducts translesion synthesis 
on templates containing AP and F with similar efficiencies and follows the 
"A-rule," inserting nucleotides in the order A > G > T. Translesion synthesis on 
templates containing C4-AP and L is less efficient than AP and F, and the 
preference for A insertion is reduced for L and absent for C4-AP. Extension past 
all abasic lesions (AP, F, C4-AP, and L) was significantly less efficient than 
translesion synthesis and yielded deletions caused by the base one or two 
nucleotides downstream from the lesion being used as a template, with the latter 
being favored. These results suggest that bypass of abasic lesions by Pol θ is 
highly mutagenic.