Targeting of human DNA polymerase ι to the replication machinery via interaction with PCNA Journal Article
| Authors: | Haracska, L.; Johnson, R. E.; Unk, I.; Phillips, B. B.; Hurwitz, J.; Prakash, L.; Prakash, S. |
| Article Title: | Targeting of human DNA polymerase ι to the replication machinery via interaction with PCNA |
| Abstract: | Human DNA polymerase ι(hPolι) promotes translesion synthesis by inserting nucleotides opposite highly distorting or noninstructional DNA lesions. Here, we provide evidence for the physical interaction of hPolι 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 hPolι. In the presence of these protein factors, on undamaged DNA, the efficiency (Vmax/Km) of correct nucleotide incorporation by hPoι is increased ≈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 (6-4) thymine-thymine (T-T) photoproduct and opposite an abasic site. The interaction of hPolι with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association. |
| Keywords: | dna-binding proteins; dna polymerase; dna replication; dna synthesis; dna damage; protein interaction; dna; molecular sequence data; kinetics; enzyme analysis; base sequence; binding sites; catalysis; dna primers; replication factor c; cycline; replication protein c; reaction analysis; replication protein a; oligodeoxyribonucleotides; proliferating cell nuclear antigen; reduction; dna-directed dna polymerase; humans; human; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 98 |
| Issue: | 25 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2001-12-04 |
| Start Page: | 14256 |
| End Page: | 14261 |
| Language: | English |
| DOI: | 10.1073/pnas.261560798 |
| PUBMED: | 11724965 |
| PROVIDER: | scopus |
| PMCID: | PMC64669 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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