Human replication factor C stimulates flap endonuclease 1 Journal Article
| Authors: | Cho, I. T.; Kim, D. H.; Kang, Y. H.; Lee, C. H.; Amangyelid, T.; Nguyen, T. A.; Hurwitz, J.; Seo, Y. S. |
| Article Title: | Human replication factor C stimulates flap endonuclease 1 |
| Abstract: | Flap endonuclease 1 (FEN1) is the enzyme responsible for specifically removing the flap structure produced during DNA replication, repair, and recombination. Here we report that the human replication factorC(RFC) complex stimulates the nuclease activity of human FEN1 in an ATP-independent manner. Although proliferating cell nuclear antigen is also known to stimulate FEN1, less RFC was required for comparable FEN1 stimulation. Kinetic analyses indicate that the mechanism by which RFC stimulates FEN1 is distinct from that by proliferating cell nuclear antigen. Heat-denatured RFC or its subunit retained, fully or partially, the ability to stimulate FEN1. Via systematic deletion analyses, we have defined three specific regions of RFC4 capable of stimulating FEN1. The region of RFC4 with the highest activity spans amino acids 170-194 and contains RFC box VII. Four amino acid residues (i.e. Tyr-182, Glu-188, Pro-189, and Ser-192) are especially important for FEN1 stimulatory activity. Thus, RFC, via several stimulatory motifs per molecule, potently activates FEN1. This function makes RFC a critical partner with FEN1 for the processing of eukaryotic Okazaki fragments. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; unclassified drug; gene deletion; genetics; molecular genetics; protein function; protein motif; protein analysis; metabolism; enzyme activation; amines; amino acid sequence; molecular sequence data; antigens; eukaryota; nucleic acids; molecular interaction; saccharomyces cerevisiae proteins; deletion analysis; dna replications; flap endonuclease-1; four amino acids; kinetic analysis; nuclease activity; okazaki fragments; proliferating cell nuclear antigens; replication factor c; amination; amino acids; organic acids; adenosine triphosphate; cycline; flap endonuclease; flap endonuclease 1; okazaki fragment; fen1 protein, human; protein subunit; rad27 protein, s cerevisiae; saccharomyces cerevisiae protein; single stranded dna; dna metabolism; enzyme kinetics; genome size; conformation; dna, single-stranded; flap endonucleases; nucleic acid conformation; protein subunits; replication protein c |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 284 |
| Issue: | 16 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2009-04-17 |
| Start Page: | 10387 |
| End Page: | 10399 |
| Language: | English |
| DOI: | 10.1074/jbc.M808893200 |
| PUBMED: | 19208620 |
| PROVIDER: | scopus |
| PMCID: | PMC2667726 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: JBCHA" - "Source: Scopus" |
