• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Sep 1995; 15(9): 4661–4671.
PMCID: PMC230709

Characterization of the five replication factor C genes of Saccharomyces cerevisiae.

Abstract

Replication factor C (RFC) is a five-subunit DNA polymerase accessory protein that functions as a structure-specific, DNA-dependent ATPase. The ATPase function of RFC is activated by proliferating cell nuclear antigen. RFC was originally purified from human cells on the basis of its requirement for simian virus 40 DNA replication in vitro. A functionally homologous protein complex from Saccharomyces cerevisiae, called ScRFC, has been identified. Here we report the cloning, by either peptide sequencing or by sequence similarity to the human cDNAs, of the S. cerevisiae genes RFC1, RFC2, RFC3, RFC4, and RFC5. The amino acid sequences are highly similar to the sequences of the homologous human RFC 140-, 37-, 36-, 40-, and 38-kDa subunits, respectively, and also show amino acid sequence similarity to functionally homologous proteins from Escherichia coli and the phage T4 replication apparatus. All five subunits show conserved regions characteristic of ATP/GTP-binding proteins and also have a significant degree of similarity among each other. We have identified eight segments of conserved amino acid sequences that define a family of related proteins. Despite their high degree of sequence similarity, all five RFC genes are essential for cell proliferation in S. cerevisiae. RFC1 is identical to CDC44, a gene identified as a cell division cycle gene encoding a protein involved in DNA metabolism. CDC44/RFC1 is known to interact genetically with the gene encoding proliferating cell nuclear antigen, confirming previous biochemical evidence of their functional interaction in DNA replication.

Full Text

The Full Text of this article is available as a PDF (1.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bell SP, Kobayashi R, Stillman B. Yeast origin recognition complex functions in transcription silencing and DNA replication. Science. 1993 Dec 17;262(5141):1844–1849. [PubMed]
  • Blanco L, Bernad A, Blasco MA, Salas M. A general structure for DNA-dependent DNA polymerases. Gene. 1991 Apr;100:27–38. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Burbelo PD, Utani A, Pan ZQ, 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. [PMC free article] [PubMed]
  • Burgers PM. Saccharomyces cerevisiae replication factor C. II. Formation and activity of complexes with the proliferating cell nuclear antigen and with DNA polymerases delta and epsilon. J Biol Chem. 1991 Nov 25;266(33):22698–22706. [PubMed]
  • Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol. 1993 Oct;13(10):6012–6023. [PMC free article] [PubMed]
  • Chen M, Pan ZQ, Hurwitz J. Sequence and expression in Escherichia coli of the 40-kDa subunit of activator 1 (replication factor C) of HeLa cells. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2516–2520. [PMC free article] [PubMed]
  • Chen M, Pan ZQ, Hurwitz J. Studies of the cloned 37-kDa subunit of activator 1 (replication factor C) of HeLa cells. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5211–5215. [PMC free article] [PubMed]
  • de Murcia G, Ménissier de Murcia J. Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem Sci. 1994 Apr;19(4):172–176. [PubMed]
  • Dong Z, Onrust R, Skangalis M, O'Donnell M. DNA polymerase III accessory proteins. I. holA and holB encoding delta and delta'. J Biol Chem. 1993 Jun 5;268(16):11758–11765. [PubMed]
  • Eki T, Matsumoto T, Murakami Y, Hurwitz J. The replication of DNA containing the simian virus 40 origin by the monopolymerase and dipolymerase systems. J Biol Chem. 1992 Apr 15;267(11):7284–7294. [PubMed]
  • Fien K, Stillman B. Identification of replication factor C from Saccharomyces cerevisiae: a component of the leading-strand DNA replication complex. Mol Cell Biol. 1992 Jan;12(1):155–163. [PMC free article] [PubMed]
  • Flower AM, McHenry CS. The adjacent dnaZ and dnaX genes of Escherichia coli are contained within one continuous open reading frame. Nucleic Acids Res. 1986 Oct 24;14(20):8091–8101. [PMC free article] [PubMed]
  • Helliwell SB, Wagner P, Kunz J, Deuter-Reinhard M, Henriquez R, Hall MN. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol Biol Cell. 1994 Jan;5(1):105–118. [PMC free article] [PubMed]
  • Howell EA, McAlear MA, Rose D, Holm C. CDC44: a putative nucleotide-binding protein required for cell cycle progression that has homology to subunits of replication factor C. Mol Cell Biol. 1994 Jan;14(1):255–267. [PMC free article] [PubMed]
  • Ittel ME, Garnier JM, Jeltsch JM, Niedergang CP. Chicken poly(ADP-ribose) synthetase: complete deduced amino acid sequence and comparison with mammalian enzyme sequences. Gene. 1991 Jun 30;102(2):157–164. [PubMed]
  • Jones EW. Tackling the protease problem in Saccharomyces cerevisiae. Methods Enzymol. 1991;194:428–453. [PubMed]
  • Kouprina N, Tsouladze A, Koryabin M, Hieter P, Spencer F, Larionov V. Identification and genetic mapping of CHL genes controlling mitotic chromosome transmission in yeast. Yeast. 1993 Jan;9(1):11–19. [PubMed]
  • Kovalic D, Kwak JH, Weisblum B. General method for direct cloning of DNA fragments generated by the polymerase chain reaction. Nucleic Acids Res. 1991 Aug 25;19(16):4560–4560. [PMC free article] [PubMed]
  • Krishna TS, Kong XP, Gary S, Burgers PM, Kuriyan J. Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell. 1994 Dec 30;79(7):1233–1243. [PubMed]
  • Lauer G, Rudd EA, McKay DL, Ally A, Ally D, Backman KC. Cloning, nucleotide sequence, and engineered expression of Thermus thermophilus DNA ligase, a homolog of Escherichia coli DNA ligase. J Bacteriol. 1991 Aug;173(16):5047–5053. [PMC free article] [PubMed]
  • Lee SH, Hurwitz J. Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5672–5676. [PMC free article] [PubMed]
  • Lee SH, Kwong AD, Pan ZQ, 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]
  • Li X, Burgers PM. 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]
  • Li X, Burgers PM. 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. [PMC free article] [PubMed]
  • Li X, Yoder BL, Burgers PM. A Saccharomyces cerevisiae DNA helicase associated with replication factor C. J Biol Chem. 1992 Dec 15;267(35):25321–25327. [PubMed]
  • Linder P, Lasko PF, Ashburner M, Leroy P, Nielsen PJ, Nishi K, Schnier J, Slonimski PP. Birth of the D-E-A-D box. Nature. 1989 Jan 12;337(6203):121–122. [PubMed]
  • Lu Y, Riegel AT. The human DNA-binding protein, PO-GA, is homologous to the large subunit of mouse replication factor C: regulation by alternate 3' processing of mRNA. Gene. 1994 Aug 5;145(2):261–265. [PubMed]
  • Luckow B, Bunz F, Stillman B, Lichter P, Schütz G. Cloning, expression, and chromosomal localization of the 140-kilodalton subunit of replication factor C from mice and humans. Mol Cell Biol. 1994 Mar;14(3):1626–1634. [PMC free article] [PubMed]
  • Matsumoto Y, Kim K, Bogenhagen DF. Proliferating cell nuclear antigen-dependent abasic site repair in Xenopus laevis oocytes: an alternative pathway of base excision DNA repair. Mol Cell Biol. 1994 Sep;14(9):6187–6197. [PMC free article] [PubMed]
  • McAlear MA, Howell EA, Espenshade KK, Holm C. Proliferating cell nuclear antigen (pol30) mutations suppress cdc44 mutations and identify potential regions of interaction between the two encoded proteins. Mol Cell Biol. 1994 Jul;14(7):4390–4397. [PMC free article] [PubMed]
  • Moir D, Stewart SE, Osmond BC, Botstein D. Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies. Genetics. 1982 Apr;100(4):547–563. [PMC free article] [PubMed]
  • Noskov V, Maki S, Kawasaki Y, Leem SH, 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. [PMC free article] [PubMed]
  • O'Donnell M, Onrust R, Dean FB, 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. [PMC free article] [PubMed]
  • Ogas J, Andrews BJ, Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. [PubMed]
  • Ogasawara N, Nakai S, Yoshikawa H. Systematic sequencing of the 180 kilobase region of the Bacillus subtilis chromosome containing the replication origin. DNA Res. 1994;1(1):1–14. [PubMed]
  • Onrust R, Stukenberg PT, O'Donnell M. Analysis of the ATPase subassembly which initiates processive DNA synthesis by DNA polymerase III holoenzyme. J Biol Chem. 1991 Nov 15;266(32):21681–21686. [PubMed]
  • Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A. Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature. 1989 Sep 21;341(6239):209–214. [PubMed]
  • Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A. Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J. 1990 Aug;9(8):2351–2359. [PMC free article] [PubMed]
  • Pause A, Sonenberg N. Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF-4A. EMBO J. 1992 Jul;11(7):2643–2654. [PMC free article] [PubMed]
  • Podust VN, Georgaki A, Strack B, Hübscher U. Calf thymus RF-C as an essential component for DNA polymerase delta and epsilon holoenzymes function. Nucleic Acids Res. 1992 Aug 25;20(16):4159–4165. [PMC free article] [PubMed]
  • Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B. The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature. 1987 Apr 2;326(6112):471–475. [PubMed]
  • Sherman F, Hicks J. Micromanipulation and dissection of asci. Methods Enzymol. 1991;194:21–37. [PubMed]
  • Shivji KK, Kenny MK, Wood RD. Proliferating cell nuclear antigen is required for DNA excision repair. Cell. 1992 Apr 17;69(2):367–374. [PubMed]
  • Spencer F, Gerring SL, Connelly C, Hieter P. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. Genetics. 1990 Feb;124(2):237–249. [PMC free article] [PubMed]
  • Spicer EK, Nossal NG, Williams KR. Bacteriophage T4 gene 44 DNA polymerase accessory protein. Sequences of gene 44 and its protein product. J Biol Chem. 1984 Dec 25;259(24):15425–15432. [PubMed]
  • Stillman B. Smart machines at the DNA replication fork. Cell. 1994 Sep 9;78(5):725–728. [PubMed]
  • Stukenberg PT, Turner J, O'Donnell M. An explanation for lagging strand replication: polymerase hopping among DNA sliding clamps. Cell. 1994 Sep 9;78(5):877–887. [PubMed]
  • Tsuchihashi Z, Kornberg A. ATP interactions of the tau and gamma subunits of DNA polymerase III holoenzyme of Escherichia coli. J Biol Chem. 1989 Oct 25;264(30):17790–17795. [PubMed]
  • Tsurimoto T, Fairman MP, Stillman B. Simian virus 40 DNA replication in vitro: identification of multiple stages of initiation. Mol Cell Biol. 1989 Sep;9(9):3839–3849. [PMC free article] [PubMed]
  • Tsurimoto T, Melendy T, Stillman B. Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin. Nature. 1990 Aug 9;346(6284):534–539. [PubMed]
  • Tsurimoto T, Stillman B. Purification of a cellular replication factor, RF-C, that is required for coordinated synthesis of leading and lagging strands during simian virus 40 DNA replication in vitro. Mol Cell Biol. 1989 Feb;9(2):609–619. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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]
  • Tsurimoto T, Stillman B. Replication factors required for SV40 DNA replication in vitro. II. Switching of DNA polymerase alpha and delta during initiation of leading and lagging strand synthesis. J Biol Chem. 1991 Jan 25;266(3):1961–1968. [PubMed]
  • Uchida K, Morita T, Sato T, Ogura T, Yamashita R, Noguchi S, Suzuki H, Nyunoya H, Miwa M, Sugimura T. Nucleotide sequence of a full-length cDNA for human fibroblast poly(ADP-ribose) polymerase. Biochem Biophys Res Commun. 1987 Oct 29;148(2):617–622. [PubMed]
  • Waga S, Stillman B. Anatomy of a DNA replication fork revealed by reconstitution of SV40 DNA replication in vitro. Nature. 1994 May 19;369(6477):207–212. [PubMed]
  • Weinberg DH, Collins KL, Simancek P, Russo A, Wold MS, Virshup DM, Kelly TJ. Reconstitution of simian virus 40 DNA replication with purified proteins. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8692–8696. [PMC free article] [PubMed]
  • Yin KC, Blinkowa A, Walker JR. Nucleotide sequence of the Escherichia coli replication gene dnaZX. Nucleic Acids Res. 1986 Aug 26;14(16):6541–6549. [PMC free article] [PubMed]
  • Yoder BL, Burgers PM. Saccharomyces cerevisiae replication factor C. I. Purification and characterization of its ATPase activity. J Biol Chem. 1991 Nov 25;266(33):22689–22697. [PubMed]
  • Young MC, Reddy MK, von Hippel PH. Structure and function of the bacteriophage T4 DNA polymerase holoenzyme. Biochemistry. 1992 Sep 22;31(37):8675–8690. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links
  • Taxonomy
    Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...