Proliferating cell nuclear antigen promotes DNA synthesis past template lesions by mammalian DNA polymerase δ

Dmitry Ju Mozzherin, Shinya Shibutani, Cheng Keat Tan, Kathleen M. Downey, Paul A. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

Consistent with previous observations, proliferating cell nuclear antigen (PCNA) promotes DNA synthesis by calf thymus DNA polymerase δ (pol δ) past several chemically defined template lesions including model abasic sites, 8-oxo-deoxyguanosine (dG) and aminofluorene-dG (but not acetylaminofluorene-dG). This synthesis is potentially mutagenic. The model abasic site was studied most extensively. When all deoxyribonucleoside triphosphates and a template bearing a model abasic site were present, DNA synthesis by pol δ beyond this site was stimulated 53-fold by addition of homologous PCNA. On an unmodified template (lacking any lesions), PCNA stimulated pol δ by 1.3-fold. Product analysis demonstrated that as expected from the 'A-rule,' fully and near-fully extended primers incorporated predominantly dAMP opposite the template lesion. Moreover, corollary primer extension studies demonstrated that in the presence (but not the absence) of PCNA, pol δ preferentially elongated primers containing dAMP opposite the model abasic template site. p21, a specific inhibitor of PCNA-dependent DNA replication, inhibits PCNA-stimulated synthesis past model abasic template sites. We propose that DNA synthesis past template lesions by pol δ promoted by PCNA results from the fundamental mechanism by which PCNA stimulates pol δ, i.e., stabilization of the pol δ-template-primer complex.

Original languageEnglish (US)
Pages (from-to)6126-6131
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number12
DOIs
StatePublished - Jun 10 1997
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Proliferating cell nuclear antigen promotes DNA synthesis past template lesions by mammalian DNA polymerase δ'. Together they form a unique fingerprint.

Cite this