期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2001
卷号:98
期号:25
页码:14256-14261
DOI:10.1073/pnas.261560798
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Human DNA polymerase {iota} (hPol{iota}) promotes translesion synthesis by inserting nucleotides opposite highly distorting or noninstructional DNA lesions. Here, we provide evidence for the physical interaction of hPol{iota} 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 hPol{iota}. In the presence of these protein factors, on undamaged DNA, the efficiency (Vmax/Km) of correct nucleotide incorporation by hPol{iota} is increased {approx}80-150-fold, and this increase in efficiency results from a reduction in the apparent Km for the nucleotide. PCNA, RFC, and RPA also stimulate nucleotide incorporation opposite the 3'-T of the (6) thymine-thymine (T-T) photoproduct and opposite an abasic site. The interaction of hPol{iota} with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association.