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Biochemistry. 1999 Sep 28;38(39):12908-14.

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

Author information

1
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.

Abstract

The effects of abasic lesions on both primase activity and DNA polymerase alpha- (pol alpha) 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 alpha resulted in 60-93% bypass of abasic lesions. Sequencing of bypass products generated during this primase-coupled pol alpha activity showed that dAMP was preferentially incorporated opposite the abasic lesion, indicating that pol alpha was responsible for bypass. In contrast, previous analyses of pol alpha-catalyzed elongation of exogenously supplied DNA primer-templates showed that abasic lesions strongly terminated DNA synthesis. Thus, elongation of primase-synthesized primers by pol alpha-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 alpha activity provides an additional mechanism for how translesional synthesis may occur in vivo, an event hypothesized to be mutagenic.

PMID:
10504262
DOI:
10.1021/bi991075m
[Indexed for MEDLINE]

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