Abstract
Replication Factor C (RFC) is a five-subunit protein complex required for eukaryotic DNA replication and repair. The large subunit within this complex contains a C-terminal DNA binding domain which provides specificity for PCNA loading at a primer-template and a second, N-terminal DNA binding domain of unknown function. We isolated the N-terminal DNA binding domain from Drosophila melanogaster and defined the region within this polypeptide required for DNA binding. The DNA determinants most efficiently recognized by both the Drosophila minimal DNA binding domain and the N-terminal half of the human large subunit consist of a double-stranded DNA containing a recessed 5' phosphate. DNA containing a recessed 5' phosphate was preferred 5-fold over hairpined DNA containing a recessed 3' hydroxyl. Combined with existing data, these DNA binding properties suggest a role for the N-terminal DNA binding domain in the recognition of phosphorylated DNA ends.
Full Text
The Full Text of this article is available as a PDF (169.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bunz F., Kobayashi R., Stillman B. cDNAs encoding the large subunit of human replication factor C. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11014–11018. doi: 10.1073/pnas.90.23.11014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burbelo P. D., Utani A., Pan Z. Q., Yamada Y. Cloning of the large subunit of activator 1 (replication factor C) reveals homology with bacterial DNA ligases. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11543–11547. doi: 10.1073/pnas.90.24.11543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burgers P. M., Kornberg A. ATP activation of DNA polymerase III holoenzyme of Escherichia coli. I. ATP-dependent formation of an initiation complex with a primed template. J Biol Chem. 1982 Oct 10;257(19):11468–11473. [PubMed] [Google Scholar]
- Cullmann G., Fien K., Kobayashi R., Stillman B. Characterization of the five replication factor C genes of Saccharomyces cerevisiae. Mol Cell Biol. 1995 Sep;15(9):4661–4671. doi: 10.1128/mcb.15.9.4661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fotedar R., Mossi R., Fitzgerald P., Rousselle T., Maga G., Brickner H., Messier H., Kasibhatla S., Hübscher U., Fotedar A. A conserved domain of the large subunit of replication factor C binds PCNA and acts like a dominant negative inhibitor of DNA replication in mammalian cells. EMBO J. 1996 Aug 15;15(16):4423–4433. [PMC free article] [PubMed] [Google Scholar]
- Halligan B. D., Teng M., Guilliams T. G., Nauert J. B., Halligan N. L. Cloning of the murine cDNA encoding VDJP, a protein homologous to the large subunit of replication factor C and bacterial DNA ligases. Gene. 1995 Aug 19;161(2):217–222. doi: 10.1016/0378-1119(95)00299-l. [DOI] [PubMed] [Google Scholar]
- Hardin S. H., Jones L. B., Homayouni R., McCollum J. C. Octamer-primed cycle sequencing: design of an optimized primer library. Genome Res. 1996 Jun;6(6):545–550. doi: 10.1101/gr.6.6.545. [DOI] [PubMed] [Google Scholar]
- Huang C. C., Hearst J. E., Alberts B. M. Two types of replication proteins increase the rate at which T4 DNA polymerase traverses the helical regions in a single-stranded DNA template. J Biol Chem. 1981 Apr 25;256(8):4087–4094. [PubMed] [Google Scholar]
- Jarvis T. C., Newport J. W., von Hippel P. H. Stimulation of the processivity of the DNA polymerase of bacteriophage T4 by the polymerase accessory proteins. The role of ATP hydrolysis. J Biol Chem. 1991 Jan 25;266(3):1830–1840. [PubMed] [Google Scholar]
- Jones L. B., Hardin S. H. Octamer-primed cycle sequencing using dye-terminator chemistry. Nucleic Acids Res. 1998 Jun 1;26(11):2824–2826. doi: 10.1093/nar/26.11.2824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuriyan J., O'Donnell M. Sliding clamps of DNA polymerases. J Mol Biol. 1993 Dec 20;234(4):915–925. doi: 10.1006/jmbi.1993.1644. [DOI] [PubMed] [Google Scholar]
- Lee S. H., Kwong A. D., Pan Z. Q., Hurwitz J. Studies on the activator 1 protein complex, an accessory factor for proliferating cell nuclear antigen-dependent DNA polymerase delta. J Biol Chem. 1991 Jan 5;266(1):594–602. [PubMed] [Google Scholar]
- Li X., Burgers P. M. Cloning and characterization of the essential Saccharomyces cerevisiae RFC4 gene encoding the 37-kDa subunit of replication factor C. J Biol Chem. 1994 Aug 26;269(34):21880–21884. [PubMed] [Google Scholar]
- Li X., Burgers P. M. Molecular cloning and expression of the Saccharomyces cerevisiae RFC3 gene, an essential component of replication factor C. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):868–872. doi: 10.1073/pnas.91.3.868. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lu Y., Zeft A. S., Riegel A. T. Cloning and expression of a novel human DNA binding protein, PO-GA. Biochem Biophys Res Commun. 1993 Jun 15;193(2):779–786. doi: 10.1006/bbrc.1993.1693. [DOI] [PubMed] [Google Scholar]
- McAlear M. A., Tuffo K. M., Holm C. The large subunit of replication factor C (Rfc1p/Cdc44p) is required for DNA replication and DNA repair in Saccharomyces cerevisiae. Genetics. 1996 Jan;142(1):65–78. doi: 10.1093/genetics/142.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noskov V., Maki S., Kawasaki Y., Leem S. H., Ono B., Araki H., Pavlov Y., Sugino A. The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae. Nucleic Acids Res. 1994 May 11;22(9):1527–1535. doi: 10.1093/nar/22.9.1527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell M., Onrust R., Dean F. B., Chen M., Hurwitz J. Homology in accessory proteins of replicative polymerases--E. coli to humans. Nucleic Acids Res. 1993 Jan 11;21(1):1–3. doi: 10.1093/nar/21.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sancar A., Hearst J. E. Molecular matchmakers. Science. 1993 Mar 5;259(5100):1415–1420. doi: 10.1126/science.8451638. [DOI] [PubMed] [Google Scholar]
- Stukenberg P. T., Studwell-Vaughan P. S., O'Donnell M. Mechanism of the sliding beta-clamp of DNA polymerase III holoenzyme. J Biol Chem. 1991 Jun 15;266(17):11328–11334. [PubMed] [Google Scholar]
- Tsurimoto T., Stillman B. Functions of replication factor C and proliferating-cell nuclear antigen: functional similarity of DNA polymerase accessory proteins from human cells and bacteriophage T4. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1023–1027. doi: 10.1073/pnas.87.3.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsurimoto T., Stillman B. Replication factors required for SV40 DNA replication in vitro. I. DNA structure-specific recognition of a primer-template junction by eukaryotic DNA polymerases and their accessory proteins. J Biol Chem. 1991 Jan 25;266(3):1950–1960. [PubMed] [Google Scholar]
- Uchiumi F., Ohta T., Tanuma S. Replication factor C recognizes 5'-phosphate ends of telomeres. Biochem Biophys Res Commun. 1996 Dec 4;229(1):310–315. doi: 10.1006/bbrc.1996.1798. [DOI] [PubMed] [Google Scholar]
- Uhlmann F., Cai J., Gibbs E., O'Donnell M., Hurwitz J. Deletion analysis of the large subunit p140 in human replication factor C reveals regions required for complex formation and replication activities. J Biol Chem. 1997 Apr 11;272(15):10058–10064. doi: 10.1074/jbc.272.15.10058. [DOI] [PubMed] [Google Scholar]
- Vinson C. R., LaMarco K. L., Johnson P. F., Landschulz W. H., McKnight S. L. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage. Genes Dev. 1988 Jul;2(7):801–806. doi: 10.1101/gad.2.7.801. [DOI] [PubMed] [Google Scholar]