Abasic template lesions are strong chain terminators for DNA primase but not for DNA polymerase alpha during the synthesis of new DNA strands

The effects of abasic lesions on both primase activity and DNA polymerase a lpha- (pol alpha) catalyzed elongation of primase-synthesized primers were examined. Abasic lesions were strong chain terminators during primer synthe sis by primase, However, extension of primase-synthesized primers by pol al pha resulted in 60-93% bypass of abasic lesions. Sequencing of bypass produ cts generated during this primase-coupled pol alpha activity showed that dA MP was preferentially incorporated opposite the abasic lesion, indicating t hat pol alpha was responsible for bypass. In contrast, previous analyses of pol alpha-catalyzed elongation of exogenously supplied DNA primer-template s showed that abasic lesions strongly terminated DNA synthesis. Thus, elong ation of primase-synthesized primers by pol alpha-primase is fundamentally different than elongation of exogenously added primer-templates with respec t to interaction with abasic lesions. Furthermore, this high level of abasi c lesion bypass during primase-coupled pol alpha activity provides an addit ional mechanism for how translesional synthesis may occur in vivo, an event hypothesized to be mutagenic.