A single domain in human DNA polymerase ι mediates interaction with PCNA: Implications for translesion DNA synthesis Journal Article
| Authors: | Haracska, L.; Acharya, N.; Unk, I.; Johnson, R. E.; Hurwitz, J.; Prakash, L.; Prakash, S. |
| Article Title: | A single domain in human DNA polymerase ι mediates interaction with PCNA: Implications for translesion DNA synthesis |
| Abstract: | DNA polymerases (Pols) of the Y family rescue stalled replication forks by promoting replication through DNA lesions. Humans have four Y family Pols, η, ι, κ, and Rev1, of which Pols η, ι, and κ have been shown to physically interact with proliferating cell nuclear antigen (PCNA) and be functionally stimulated by it. However, in sharp contrast to the large increase in processivity that PCNA binding imparts to the replicative Pol, Polδ, the processivity of Y family Pols is not enhanced upon PCNA binding. Instead, PCNA binding improves the efficiency of nucleotide incorporation via a reduction in the apparent K m for the nucleotide. Here we show that Polι interacts with PCNA via only one of its conserved PCNA binding motifs, regardless of whether PCNA is bound to DNA or not. The mode of PCNA binding by Polι is quite unlike that in Polδ, where multisite interactions with PCNA provide for a very tight binding of the replicating Pol with PCNA. We discuss the implications of these observations for the accuracy of DNA synthesis during translesion synthesis and for the process of Pol exchange at the lesion site. |
| Keywords: | unclassified drug; gene mutation; nonhuman; dna polymerase; dna replication; dna synthesis; protein motif; protein protein interaction; protein binding; dna; amino acid sequence; molecular sequence data; protein purification; nucleotide sequence; escherichia coli; recombinant proteins; models, molecular; cycline; enzyme subunit; two hybrid system; amino acid motifs; proliferating cell nuclear antigen; dna-directed dna polymerase; dna directed dna polymerase delta; negibacteria; dna polymerase iii; dna polymerase iota |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 25 |
| Issue: | 3 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2005-02-01 |
| Start Page: | 1183 |
| End Page: | 1190 |
| Language: | English |
| DOI: | 10.1128/mcb.25.3.1183-1190.2005 |
| PUBMED: | 15657443 |
| PROVIDER: | scopus |
| PMCID: | PMC544020 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 24 October 2012" - "CODEN: MCEBD" - "Source: Scopus" |
