Abasic Template Lesions Are Strong Chain Terminators for DNA Primase but Not for DNA Polymerase α during the Synthesis of New DNA Strands

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Abstract
The effects of abasic lesions on both primase activity and DNA polymerase α- (pol α) catalyzed elongation of primase-synthesized primers were examined. Abasic lesions were strong chain terminators during primer synthesis by primase. However, extension of primase-synthesized primers by pol α resulted in 60−93% bypass of abasic lesions. Sequencing of bypass products generated during this primase-coupled pol α activity showed that dAMP was preferentially incorporated opposite the abasic lesion, indicating that pol α was responsible for bypass. In contrast, previous analyses of pol α-catalyzed elongation of exogenously supplied DNA primer−templates showed that abasic lesions strongly terminated DNA synthesis. Thus, elongation of primase-synthesized primers by pol α−primase is fundamentally different than elongation of exogenously added primer−templates with respect to interaction with abasic lesions. Furthermore, this high level of abasic lesion bypass during primase-coupled pol α activity provides an additional mechanism for how translesional synthesis may occur in vivo, an event hypothesized to be mutagenic.

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