PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of narLink to Publisher's site
 
Nucleic Acids Res. 1998 September 1; 26(17): 3925–3932.
PMCID: PMC147798

PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain.

Abstract

The eukaryotic polymerase processivity factor, PCNA, interacts with cell cycle regulatory proteins such as p21(WAF1/Cip1) and Gadd45, as well as with proteins involved in the mechanics of DNA repair and replication. A conserved PCNA-binding motif is found in a subset of PCNA-interacting proteins, including p21, suggesting that the regulation of these interactions is important for the co-ordination of DNA replication and repair. We have identified several classes of protein which bind to Drosophila PCNA. Two of these proteins contain the consensus PCNA-binding domain: one is the Dacapo protein, a Drosophila homologue of p21(WAF1/Cip1), and the second is the transposase encoded by the Pogo DNA transposon . A conserved PCNA-binding domain is also present in a human relative of Pogo , named Tigger , suggesting that this domain has a functional role in this class of transposable element. This raises interesting possibilities for a novel method of transposition in which the transposase might be targeted to replicating DNA. Finally, we have investigated the use of this conserved PCNA-binding domain as a predictor of PCNA-binding capacity.

Full Text

The Full Text of this article is available as a PDF (467K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kelman Z. PCNA: structure, functions and interactions. Oncogene. 1997 Feb 13;14(6):629–640. [PubMed]
  • Jónsson ZO, Hübscher U. Proliferating cell nuclear antigen: more than a clamp for DNA polymerases. Bioessays. 1997 Nov;19(11):967–975. [PubMed]
  • Olsen GJ, Woese CR. Archaeal genomics: an overview. Cell. 1997 Jun 27;89(7):991–994. [PubMed]
  • Kong XP, Onrust R, O'Donnell M, Kuriyan J. Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp. Cell. 1992 May 1;69(3):425–437. [PubMed]
  • Hindges R, Hübscher U. DNA polymerase delta, an essential enzyme for DNA transactions. Biol Chem. 1997 May;378(5):345–362. [PubMed]
  • Lee SH, Pan ZQ, Kwong AD, Burgers PM, Hurwitz J. Synthesis of DNA by DNA polymerase epsilon in vitro. J Biol Chem. 1991 Nov 25;266(33):22707–22717. [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]
  • Nichols AF, Sancar A. Purification of PCNA as a nucleotide excision repair protein. Nucleic Acids Res. 1992 Jul 11;20(13):2441–2446. [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]
  • Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994 Jun 16;369(6481):574–578. [PubMed]
  • Flores-Rozas H, Kelman Z, Dean FB, Pan ZQ, Harper JW, Elledge SJ, O'Donnell M, Hurwitz J. Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8655–8659. [PubMed]
  • Warbrick E, Lane DP, Glover DM, Cox LS. A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol. 1995 Mar 1;5(3):275–282. [PubMed]
  • Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS. Characterisation of the interaction between PCNA and Gadd45. Oncogene. 1995 Jun 15;10(12):2427–2433. [PubMed]
  • Henderson DS, Banga SS, Grigliatti TA, Boyd JB. Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA. EMBO J. 1994 Mar 15;13(6):1450–1459. [PubMed]
  • Yamaguchi M, Nishida Y, Moriuchi T, Hirose F, Hui CC, Suzuki Y, Matsukage A. Drosophila proliferating cell nuclear antigen (cyclin) gene: structure, expression during development, and specific binding of homeodomain proteins to its 5'-flanking region. Mol Cell Biol. 1990 Mar;10(3):872–879. [PMC free article] [PubMed]
  • Lane ME, Sauer K, Wallace K, Jan YN, Lehner CF, Vaessin H. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell. 1996 Dec 27;87(7):1225–1235. [PubMed]
  • de Nooij JC, Letendre MA, Hariharan IK. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell. 1996 Dec 27;87(7):1237–1247. [PubMed]
  • Tudor M, Lobocka M, Goodell M, Pettitt J, O'Hare K. The pogo transposable element family of Drosophila melanogaster. Mol Gen Genet. 1992 Mar;232(1):126–134. [PubMed]
  • Warbrick E, Lane DP, Glover DM, Cox LS. Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair. Oncogene. 1997 May 15;14(19):2313–2321. [PubMed]
  • Li X, Li J, Harrington J, Lieber MR, Burgers PM. Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen. J Biol Chem. 1995 Sep 22;270(38):22109–22112. [PubMed]
  • Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS. The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. J Biol Chem. 1997 Sep 26;272(39):24522–24529. [PubMed]
  • Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science. 1997 Sep 26;277(5334):1996–2000. [PubMed]
  • Smit AF, Riggs AD. Tiggers and DNA transposon fossils in the human genome. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1443–1448. [PubMed]
  • Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. [PMC free article] [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Durfee T, Becherer K, Chen PL, Yeh SH, Yang Y, Kilburn AE, Lee WH, Elledge SJ. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. [PubMed]
  • Koepp DM, Silver PA. A GTPase controlling nuclear trafficking: running the right way or walking RANdomly? Cell. 1996 Oct 4;87(1):1–4. [PubMed]
  • Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993 Apr 22;362(6422):709–715. [PubMed]
  • Nilsen H, Otterlei M, Haug T, Solum K, Nagelhus TA, Skorpen F, Krokan HE. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic Acids Res. 1997 Feb 15;25(4):750–755. [PMC free article] [PubMed]
  • Slupphaug G, Olsen LC, Helland D, Aasland R, Krokan HE. Cell cycle regulation and in vitro hybrid arrest analysis of the major human uracil-DNA glycosylase. Nucleic Acids Res. 1991 Oct 11;19(19):5131–5137. [PMC free article] [PubMed]
  • Bravo R, Macdonald-Bravo H. Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987 Oct;105(4):1549–1554. [PMC free article] [PubMed]
  • Li R, Hannon GJ, Beach D, Stillman B. Subcellular distribution of p21 and PCNA in normal and repair-deficient cells following DNA damage. Curr Biol. 1996 Feb 1;6(2):189–199. [PubMed]
  • Leonhardt H, Page AW, Weier HU, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell. 1992 Nov 27;71(5):865–873. [PubMed]
  • Lasko DD, Tomkinson AE, Lindahl T. Mammalian DNA ligases. Biosynthesis and intracellular localization of DNA ligase I. J Biol Chem. 1990 Jul 25;265(21):12618–12622. [PubMed]
  • Tomkinson AE, Levin DS. Mammalian DNA ligases. Bioessays. 1997 Oct;19(10):893–901. [PubMed]
  • Montecucco A, Savini E, Weighardt F, Rossi R, Ciarrocchi G, Villa A, Biamonti G. The N-terminal domain of human DNA ligase I contains the nuclear localization signal and directs the enzyme to sites of DNA replication. EMBO J. 1995 Nov 1;14(21):5379–5386. [PubMed]
  • Cardoso MC, Joseph C, Rahn HP, Reusch R, Nadal-Ginard B, Leonhardt H. Mapping and use of a sequence that targets DNA ligase I to sites of DNA replication in vivo. J Cell Biol. 1997 Nov 3;139(3):579–587. [PMC free article] [PubMed]
  • Levin DS, Bai W, Yao N, O'Donnell M, Tomkinson AE. An interaction between DNA ligase I and proliferating cell nuclear antigen: implications for Okazaki fragment synthesis and joining. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12863–12868. [PubMed]
  • Jónsson ZO, Hindges R, Hübscher U. Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen. EMBO J. 1998 Apr 15;17(8):2412–2425. [PubMed]
  • Xiong Y, Zhang H, Beach D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell. 1992 Oct 30;71(3):505–514. [PubMed]
  • Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E, et al. Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell. 1995 Apr;6(4):387–400. [PMC free article] [PubMed]
  • Goubin F, Ducommun B. Identification of binding domains on the p21Cip1 cyclin-dependent kinase inhibitor. Oncogene. 1995 Jun 15;10(12):2281–2287. [PubMed]
  • LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997 Apr 1;11(7):847–862. [PubMed]
  • Chen U, Chen S, Saha P, Dutta A. p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11597–11602. [PubMed]
  • Ball KL, Lain S, Fâhraeus R, Smythe C, Lane DP. Cell-cycle arrest and inhibition of Cdk4 activity by small peptides based on the carboxy-terminal domain of p21WAF1. Curr Biol. 1997 Jan 1;7(1):71–80. [PubMed]
  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995 Oct 12;377(6549):552–557. [PubMed]
  • van Luenen HG, Colloms SD, Plasterk RH. The mechanism of transposition of Tc3 in C. elegans. Cell. 1994 Oct 21;79(2):293–301. [PubMed]
  • Kachroo P, Leong SA, Chattoo BB. Pot2, an inverted repeat transposon from the rice blast fungus Magnaporthe grisea. Mol Gen Genet. 1994 Nov 1;245(3):339–348. [PubMed]
  • Daboussi MJ, Langin T, Brygoo Y. Fot1, a new family of fungal transposable elements. Mol Gen Genet. 1992 Mar;232(1):12–16. [PubMed]
  • Hohmann S. Characterisation of PDC2, a gene necessary for high level expression of pyruvate decarboxylase structural genes in Saccharomyces cerevisiae. Mol Gen Genet. 1993 Dec;241(5-6):657–666. [PubMed]
  • Prior C, Tizzani L, Fukuhara H, Wésolowski-Louvel M. RAG3 gene and transcriptional regulation of the pyruvate decarboxylase gene in Kluyveromyces lactis. Mol Microbiol. 1996 May;20(4):765–772. [PubMed]
  • Toth M, Grimsby J, Buzsaki G, Donovan GP. Epileptic seizures caused by inactivation of a novel gene, jerky, related to centromere binding protein-B in transgenic mice. Nat Genet. 1995 Sep;11(1):71–75. [PubMed]
  • Earnshaw WC, Sullivan KF, Machlin PS, Cooke CA, Kaiser DA, Pollard TD, Rothfield NF, Cleveland DW. Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen. J Cell Biol. 1987 Apr;104(4):817–829. [PMC free article] [PubMed]
  • Warbrick E. PCNA binding through a conserved motif. Bioessays. 1998 Mar;20(3):195–199. [PubMed]
  • Percival KJ, Klein MB, Burgers PM. Molecular cloning and primary structure of the uracil-DNA-glycosylase gene from Saccharomyces cerevisiae. J Biol Chem. 1989 Feb 15;264(5):2593–2598. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press