Disease relevance of RFC1

• Therefore, at least two subunits in RFC make strong contacts with PCNA, unlike the Escherichia coli gamma complex in which only one subunit makes strong contact with the beta clamp [1].
• The RFC1 gene was cloned under control of the strong inducible bacteriophage T7 promoter, yet induction did not yield detectable Rfc1p [2].
• It also interacts with several host proteins, including the cell cycle regulator, retinoblastoma, and essential components of the cell DNA replication machinery, like proliferating nuclear cell antigen (PCNA) and RFC-1 [3].

High impact information on RFC1

• Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C [4].
• We report that Ctf18, Ctf8, and Dcc1, the subunits of a Replication Factor C (RFC)-like complex, are essential for the perinuclear positioning of telomeres [5].
• We propose that Elg1-RFC functions both in normal DNA replication and in the DNA damage response [6].
• This complex is distinct from the DNA replication RFC, the DNA damage checkpoint RFC and the sister chromatid cohesion RFC [6].
• Elg1 forms an alternative RFC complex important for DNA replication and genome integrity [6].

Biological context of RFC1

• Replacement of RFC1 by rfc1-DeltaN in yeast shows essentially no phenotype with regard to DNA replication, damage susceptibility, telomere length maintenance, and intrachromosomal recombination [2].
• The RFC5 gene encodes a small subunit of replication factor C (RFC) complex in Saccharomyces cerevisiae and has been shown to be required for the checkpoints which respond to replication block and DNA damage [7].
• Both the RFC subunits and Rad24 contain a consensus sequence for nucleoside triphosphate (NTP) binding [8].
• RFC1 is identical to CDC44, a gene identified as a cell division cycle gene encoding a protein involved in DNA metabolism [9].
• Replication factor C is required to load proliferating cell nuclear antigen onto primer-template junctions, using the energy of ATP hydrolysis [10].

Anatomical context of RFC1

• Calf thymus PCNA also stimulated the ATPase activity of yeast RF-C and participated in holoenzyme formation with DNA polymerase delta [11].
• Replication and related processes in eukaryotic cells require replication factor C (RFC) to load a molecular clamp for DNA polymerase in an ATP-driven process, involving multiple molecular interactions [12].
• Sequence analysis of a 30 kb DNA segment from yeast chromosome XIV carrying a ribosomal protein gene cluster, the genes encoding a plasma membrane protein and a subunit of replication factor C, and a novel putative serine/threonine protein kinase gene [13].
• Transcripts of the genes ARFC3, encoding a component of the replication factor C, and GAA, encoding a secretory glucoamylase, can be detected only in cells cultured in media with NaCl concentrations below 10% [14].

Associations of RFC1 with chemical compounds

• Binding of adenosine (3-thiotriphosphate) (ATPgammaS), a nonhydrolyzable analog of ATP, to replication factor C with a N-terminal truncation (Delta2-273) of the Rfc1 subunit (RFC) was studied by filter binding [15].
• Analysis of their functions, along with previously prepared alanine scanning mutants, demonstrated that some loops interact with DNA polymerase delta (pol delta) and replication factor C (RFC) [16].
• Surprisingly, the helicase could be separated from RF-C by sedimentation on a glycerol gradient in the presence of 200 mM NaCl [17].
• This DNA helicase co-purified with replication factor C (RF-C) during chromatography on S-Sepharose, DEAE-silica gel high performance liquid chromatography (HPLC), Affi-Gel Blue-agarose, heparin-agarose, single-stranded DNA-cellulose, fast protein liquid chromatography MonoS, and hydroxyapatite HPLC [17].

Physical interactions of RFC1

• The RFC1 subunit also binds PCNA tightly, and we identify two hydrophobic residues in RFC1 that are important for this interaction [1].
• A novel Rad24 checkpoint protein complex closely related to replication factor C [18].
• Furthermore, the Rfc2 protein was copurified with RF-C activity throughout RF-C purification [19].
• Ctf8p is a component of Ctf18-RFC, an alternative replication factor C-like complex required for efficient sister chromatid cohesion in Saccharomyces cerevisiae [20].

Enzymatic interactions of RFC1

• Replication factor C (RFC) catalyzes assembly of circular proliferating cell nuclear antigen clamps around primed DNA, enabling processive synthesis by DNA polymerase during DNA replication and repair [21].

Regulatory relationships of RFC1

• Proliferating cell nuclear antigen (pol30) mutations suppress cdc44 mutations and identify potential regions of interaction between the two encoded proteins [22].

Other interactions of RFC1

• The PCNA-RFC families of DNA clamps and clamp loaders [23].
• Mechanical link between cohesion establishment and DNA replication: Ctf7p/Eco1p, a cohesion establishment factor, associates with three different replication factor C complexes [24].
• Rfc5, a replication factor C component, is required for regulation of Rad53 protein kinase in the yeast checkpoint pathway [25].
• Cloning and characterization of the essential Saccharomyces cerevisiae RFC4 gene encoding the 37-kDa subunit of replication factor C [26].
• The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae [19].

Analytical, diagnostic and therapeutic context of RFC1

• Reciprocal co-immunoprecipitation studies were performed using extracts prepared from strains containing epitope-tagged RFC proteins [18].
• Site-directed mutagenesis has been used to demonstrate the biological significance of the RF-C/activator 1-related domains [27].
• Molecular cloning and expression of the Saccharomyces cerevisiae RFC3 gene, an essential component of replication factor C [28].
• The second round of two-hybrid assay with Lin1p as the bait resulted in the identification of six proteins: Prp8, Slx5, Siz2, Wss1, Rfc1 and YIL149w [29].
• DNA helicase D co-purified with Replication Factor C over seven chromatographic steps, and was only separated from it by glycerol gradient centrifugation in the presence of 0.2 M NaCl [30].

References