Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 98, Issue 25, Pages 14256-14261Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.261560798
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- NIGMS NIH HHS [GM38559, GM19261] Funding Source: Medline
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Human DNA polymerase i (hPoli) promotes translesion synthesis by inserting nucleotides opposite highly distorting or noninstructional DNA lesions. Here, we provide evidence for the physical interaction of hPoli with proliferating cell nuclear antigen (PCNA), and show that PCNA, together with replication factor C (RFC) and replication protein A (RPA), stimulates the DNA synthetic activity of hPoli. In the presence of these protein factors, on undamaged DNA, the efficiency (V-max/K-m) of correct nucleotide incorporation by hPoli is increased approximate to 80-150-fold, and this increase in efficiency results from a reduction in the apparent K-m for the nucleotide. PCNA, RFC, and RPA also stimulate nucleotide incorporation opposite the 3'-T of the (6-4) thymine-thymine (T-T) photoproduct and opposite an abasic site. The interaction of hPoli with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association.
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