ATP hydrolysis catalyzed by human replication factor C requires participation of multiple subunits Journal Article
| Authors: | Cai, J.; Yao, N.; Gibbs, E.; Finkelstein, J.; Phillips, B.; O'Donnell, M.; Hurwitz, J. |
| Article Title: | ATP hydrolysis catalyzed by human replication factor C requires participation of multiple subunits |
| Abstract: | Human replication factor C (hRFC) is a five-subunit protein complex (p140, p40, p38, p37, and p36) that acts to catalytically load proliferating cell nuclear antigen onto DNA, where it recruits DNA polymerase δ or ε to the primer terminus at the expense of ATP, leading to processive DNA synthesis. We have previously shown that a subcomplex of hRFC consisting of three subunits (p40, p37, and p36) contained DNA-dependent ATPase activity. However, it is not clear which subunit(s) hydrolyzes ATP, as all five subunits include potential ATP binding sites. In this report, we introduced point mutations in the putative ATP-binding sequences of each hRFC subunit and examined the properties of the resulting mutant hRFC complex and the ATPase activity of the hRFC or the p40·p37·p36 complex. A mutation in any one of the ATP binding sites of the p36, p37, p40, or p140 subunits markedly reduced replication activity of the hRFC complex and the ATPase activity of the hRFC or the p40·p37·p36 complex. A mutation in the ATP binding site of the p38 subunit did not alter the replication activity of hRFC. These findings indicate that the replication activity of hRFC is dependent on efficient ATP hydrolysis contributed to by the action of four hRFC subunits. |
| Keywords: | dna-binding proteins; nonhuman; dna polymerase; dna replication; dna synthesis; protein conformation; models, biological; homeodomain proteins; dna; amino acid sequence; energy transfer; binding site; mutagenesis, site-directed; binding sites; saccharomyces cerevisiae proteins; adenosine triphosphate; cycline; replication protein c; point mutation; adenosine triphosphatase; repressor proteins; proto-oncogene proteins c-bcl-2; hydrolysis; proliferating cell nuclear antigen; humans; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 95 |
| Issue: | 20 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1998-09-29 |
| Start Page: | 11607 |
| End Page: | 11612 |
| Language: | English |
| DOI: | 10.1073/pnas.95.20.11607 |
| PUBMED: | 9751713 |
| PROVIDER: | scopus |
| PMCID: | PMC21688 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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