Skip to main content
SpringerLink
Log in

His-Cys Box Homing Endonucleases

  • Chapter
Homing Endonucleases and Inteins

Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 16))

Abstract

Homing endonucleases are often grouped into four families based on distinct sequence motifs. One of these families is known as the His-Cys box homing endonucleases and contains two clusters of conserved histidine and cysteine residues over a central 100 amino acid region. At last count, 23 members of this family had been identified. The open reading frames (ORFs) of these proteins are contained within mobile group I introns found in nuclear rDNA genes of several protists. The nuclear location of these introns and ORFs is currently unique among the homing endonuclease families and poses an intriguing puzzle regarding their expression from non-coding rRNA transcripts.

The best-studied member of the His-Cys box homing endonucleases is I-PpoI from the myxomycete Physarum polycephalum. Following an introduction to all of the known members of the His-Cys box endonuclease family, much of the following chapter will outline the extensive characterization of I-PpoI structure and function. Although our understanding of how I-PpoI is expressed in cells is still not fully complete, the means by which I-PpoI specifically recognizes a single cleavage site in the host genome to mediate homing of its host intron is widely accepted. Details of DNA recognition and the catalytic mechanism of nucleolytic cleavage have been ascertained from both in vivo and in vitro activity assays as well as from extensive X-ray crystallographic structural analyses of the enzyme bound to its DNA substrate.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Argast GM (1998) I-PpoI and I-CreI homing site sequence degeneracy determined by random mutagenesis and sequential in vitro enrichment. J Mol Biol 280:345–353

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharya D, Friedl T, Helms G (2002) Vertical evolution and intragenic spread of lichen-fungal group I introns. J Mol Evol 55:74–84

    Article  PubMed  CAS  Google Scholar 

  • Brehm SL, Cech SL, Cech TR (1983) Fate of an intervening sequence ribonucleic acid: excision and cyclization of the Tetrahymena ribosomal ribonucleic acid intervening sequence in vivo. Biochemistry 22:2390–2397

    Article  PubMed  CAS  Google Scholar 

  • Cho Y, Qiu YL, Kuhlman P, Palmer JD (1998) Explosive invasion of plant mitochondria by a group I intron. Proc Natl Acad Sci USA 95:14244–14249

    PubMed  CAS  Google Scholar 

  • De Jonckheere JF (1994) Evidence for the ancestral origin of group I introns in the SSUrDNA of Naegleria spp. J Eukaryot Microbiol 41:457–463

    PubMed  Google Scholar 

  • De Jonckheere JF, Brown S (1998) Three different group I introns in the nuclear large subunit ribosomal DNA of the amoeboflagellate Naegleria. Nucleic Acids Res 26:456–461

    PubMed  Google Scholar 

  • Decatur WA, Einvik C, Johansen S, Vogt VM (1995) Two group I ribozymes with different functions in a nuclear rDNA intron. EMBO J 14:4558–4568

    PubMed  CAS  Google Scholar 

  • Decatur WA, Johansen S, Vogt VM (2000) Expression of the Naegleria intron endonuclease is dependent on a functional group I self-cleaving ribozyme. RNA 6:616–627

    Article  PubMed  CAS  Google Scholar 

  • Drouin M, Lucas P, Otis C, Lemieux C, Turmel M (2000) Biochemical characterization of I-CmoeI reveals that this H-N-H homing endonuclease shares functional similarities with H-N-H colicins. Nucleic Acids Res 28:4566–4572

    Article  PubMed  CAS  Google Scholar 

  • Eddy SR, Gold L (1991) The phage T4 nrdB intron: a deletion mutant of a version found in the wild. Genes Dev 5:1032–1041

    PubMed  CAS  Google Scholar 

  • Einvik C, Decatur WA, Embley TM, Vogt VM, Johansen S (1997) Naegleria nucleolar introns contain two group I ribozymes with different functions in RNA splicing and processing. RNA 3:710–720

    PubMed  CAS  Google Scholar 

  • Elde M, Haugen P, Willassen NP, Johansen S (1999) I-NjaI, a nuclear intron-encoded homing endonuclease from Naegleria, generates a pentanucleotide 3′ cleavage-overhang within a 19 base-pair partially symmetric DNA recognition site. Eur J Biochem 259:281–288

    Article  PubMed  CAS  Google Scholar 

  • Elde M, Willassen NP, Johansen S (2000) Functional characterization of isoschizomeric His-Cys box homing endonucleases from Naegleria. Eur J Biochem 267:7257–7266

    Article  PubMed  CAS  Google Scholar 

  • Ellison EL, Vogt VM (1993) Interaction of the intron-encoded mobility endonuclease I-PpoI with its target site. Mol Cell Biol 13:7531–7539

    PubMed  CAS  Google Scholar 

  • Flick KE, Jurica MS, Monnat RJ Jr, Stoddard BL (1998) DNA binding and cleavage by the nuclear intron-encoded homing endonuclease I-PpoI. Nature 394:96–101

    PubMed  CAS  Google Scholar 

  • Foley S, Bruttin A, Brussow H (2000) Widespread distribution of a group I intron and its three deletion derivatives in the lysin gene of Streptococcus thermophilus bacteriophages. J Virol 74:611–618

    Article  PubMed  CAS  Google Scholar 

  • Friedhoff P, Franke I, Meiss G, Wende W, Krause KL, Pingoud A (1999) A similar active site for non-specific and specific endonucleases. Nat Struct Biol 6:112–113

    PubMed  CAS  Google Scholar 

  • Galburt EA, Chevalier B, Tang W, Jurica MS, Flick KE, Monnat RJ Jr, Stoddard BL (1999) A novel endonuclease mechanism directly visualized for I-PpoI. Nat Struct Biol 6:1096–1099

    Article  PubMed  CAS  Google Scholar 

  • Galburt EA, Chadsey MS, Jurica MS, Chevalier BS, Erho D, Tang W, Monnat RJ Jr, Stoddard BL (2000) Conformational changes and cleavage by the homing endonuclease I-PpoI: a critical role for a leucine residue in the active site. J Mol Biol 300:877–887

    Article  PubMed  CAS  Google Scholar 

  • Goddard MR, Burt A (1999) Recurrent invasion and extinction of a selfish gene. Proc Natl Acad Sci USA 96:13880–13885

    Article  PubMed  CAS  Google Scholar 

  • Goodrich-Blair H, Shub DA (1996) Beyond homing: competition between intron endonucleases confers a selective advantage on flanking genetic markers. Cell 84:211–221

    PubMed  CAS  Google Scholar 

  • Haugen P, Huss VA, Nielsen H, Johansen S (1999) Complex group-I introns in nuclear SSU rDNA of red and green algae: evidence of homing-endonuclease pseudogenes in the Bangiophyceae. Curr Genet 36:345–353

    Article  PubMed  CAS  Google Scholar 

  • Haugen P, de Jonckheere JF, Johansen S (2002) Characterization of the self-splicing products of two complex Naegleria LSU rDNA group I introns containing homing endonuclease genes. Eur J Biochem 269:1641–1649

    Article  PubMed  CAS  Google Scholar 

  • Haugen P, Reeb V, Lutzoni F, Bhattacharya D (2004) The evolution of homing endonuclease genes and group I introns in nuclear rDNA. Mol Biol Evol 21:129–140

    PubMed  CAS  Google Scholar 

  • Johansen S, Haugen P (1999) A complex group I intron in Nectria galligena rDNA. Microbiology 145:516–517

    Article  PubMed  CAS  Google Scholar 

  • Johansen S, Vogt VM (1994) An intron in the nuclear ribosomal DNA of Didymium iridis codes for a group I ribozyme and a novel ribozyme that cooperate in self-splicing. Cell 76:725–734

    Article  PubMed  CAS  Google Scholar 

  • Johansen S, Embley TM, Willassen NP (1993) A family of nuclear homing endonucleases. Nucleic Acids Res 21:4405

    PubMed  CAS  Google Scholar 

  • Johansen S, Elde M, Vader A, Haugen P, Haugli K, Haugli F (1997) In vivo mobility of a group I twintron in nuclear ribosomal DNA of the myxomycete Didymium iridis. Mol Microbiol 24:737–745

    Article  PubMed  CAS  Google Scholar 

  • Jurica MS, Stoddard BL (1999) Homing endonucleases: structure, function and evolution. Cell Mol Life Sci 55:1304–1326

    Article  PubMed  CAS  Google Scholar 

  • Kleanthous C, Kuhlmann UC, Pommer AJ, Ferguson N, Radford SE, Moore GR, James R, Hemmings AM (1999) Structural and mechanistic basis of immunity toward endonuclease colicins. Nat Struct Biol 6:243–252

    Article  PubMed  CAS  Google Scholar 

  • Kuhlmann UC, Moore GR, James R, Kleanthous C, Hemmings AM (1999) Structural parsimony in endonuclease active sites: should the number of homing endonuclease families be redefined? FEBS Lett 463:1–2

    PubMed  CAS  Google Scholar 

  • Lambowitz AM, Belfort M (1993) Introns as mobile genetic elements. Annu Rev Biochem 62:587–622

    Article  PubMed  CAS  Google Scholar 

  • Le Hir H, Nott A, Moore MJ (2003) How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 28:215–220

    PubMed  Google Scholar 

  • Lin J, Vogt VM (1998) I-PpoI, the endonuclease encoded by the group I intron PpLSU3, is expressed from an RNA polymerase I transcript. Mol Cell Biol 18:5809–5817

    PubMed  CAS  Google Scholar 

  • Lin J, Vogt VM (2000) Functional alpha-fragment of beta-galactosidase can be expressed from the mobile group I intron PpLSU3 embedded in yeast pre-ribosomal RNA derived from the chromosomal rDNA locus. Nucleic Acids Res 28:1428–1438

    PubMed  CAS  Google Scholar 

  • Loizos N, Tillier ER, Belfort M (1994) Evolution of mobile group I introns: recognition of intron sequences by an intron-encoded endonuclease. Proc Natl Acad Sci USA 91:11983–11987

    PubMed  CAS  Google Scholar 

  • Lowery R, Hung L, Knoche K, Bandziulis R (1992) Properties of I-PpoI: a rare-cutting intron-encoded endonuclease. Promega Notes 38:8–12

    Google Scholar 

  • Maniatis T, Reed R (2002) An extensive network of coupling among gene expression machines. Nature 416:499–506

    Article  PubMed  CAS  Google Scholar 

  • Miller MD, Krause KL (1996) Identification of the Serratia endonuclease dimer: structural basis and implications for catalysis. Protein Sci 5:24–33

    PubMed  CAS  Google Scholar 

  • Mota EM, Collins RA (1988) Independent evolution of structural and coding regions in a Neurospora mitochondrial intron. Nature 332:654–656

    Article  PubMed  CAS  Google Scholar 

  • Muller KM, Cannone JJ, Gutell RR, Sheath RG (2001) A structural and phylogenetic analysis of the group IC1 introns in the order Bangiales (Rhodophyta). Mol Biol Evol 18:1654–1667

    PubMed  CAS  Google Scholar 

  • Muscarella DE, Ellison EL, Ruoff BM, Vogt VM (1990) Characterization of I-Ppo, an intron-encoded endonuclease that mediates homing of a group I intron in the ribosomal DNA of Physarum polycephalum. Mol Cell Biol 10:3386–3396

    PubMed  CAS  Google Scholar 

  • Nielsen H, Fiskaa T, Birgisdottir AB, Haugen P, Einvik C, Johansen S (2003) The ability to form full-length intron RNA circles is a general property of nuclear group I introns. RNA 9:1464–1475

    Article  PubMed  CAS  Google Scholar 

  • Nozaki H, Takahara M, Nakazawa A, Kita Y, Yamada T, Takano H, Kawano S, Kato M (2002) Evolution of rbcL group IA introns and intron open reading frames within the colonial Volvocales (Chlorophyceae). Mol Phylogenet Evol 23:326–338

    PubMed  CAS  Google Scholar 

  • Ogawa S, Naito K, Angata K, Morio T, Urushihara H, Tanaka Y (1997) A site-specific DNA endonuclease specified by one of two ORFs encoded by a group I intron in Dictyostelium discoideum mitochondrial DNA. Gene 191:115–121

    Article  PubMed  CAS  Google Scholar 

  • Pellenz S, Harington A, Dujon B, Wolf K, Schafer B (2002) Characterization of the I-Spom I endonuclease from fission yeast: insights into the evolution of a group I intron-encoded homing endonuclease. J Mol Evol 55:302–313

    Article  PubMed  CAS  Google Scholar 

  • Perotto S, Nepote-Fus P, Saletta L, Bandi C, Young JP (2000) A diverse population of introns in the nuclear ribosomal genes of ericoid mycorrhizal fungi includes elements with sequence similarity to endonuclease-coding genes. Mol Biol Evol 17:44–59

    PubMed  CAS  Google Scholar 

  • Proudfoot NJ, Furger A, Dye MJ (2002) Integrating mRNA processing with transcription. Cell 108:501–512

    Article  PubMed  CAS  Google Scholar 

  • Shen BW, Landthaler M, Shub DA, Stoddard BL (2004) DNA binding and cleavage by the HNH homing endonuclease I-HmuI. J Mol Biol 342:43–56

    Article  PubMed  CAS  Google Scholar 

  • Tanabe Y, Yokota A, Sugiyama J (2002) Group I introns from Zygomycota: evolutionary implications for the fungal IC1 intron subgroup. J Mol Evol 54:692–702

    Article  PubMed  CAS  Google Scholar 

  • Vader A (1998) Nuclear group I introns of the myxomycetes: organization, expression and evolution. University of Tromsù, Norway

    Google Scholar 

  • Vader A, Nielsen H, Johansen S (1999) In vivo expression of the nucleolar group I intron-encoded I-dirI homing endonuclease involves the removal of a spliceosomal intron. EMBO J 18:1003–1013

    Article  PubMed  CAS  Google Scholar 

  • Van Roey P, Waddling CA, Fox KM, Belfort M, Derbyshire V (2001) Intertwined structure of the DNA-binding domain of intron endonuclease I-TevI with its substrate. EMBO J 20:3631–3637

    PubMed  Google Scholar 

  • Wittmayer PK, Raines RT (1996) Substrate binding and turnover by the highly specific I-PpoI endonuclease. Biochemistry 35:1076–1083

    Article  PubMed  CAS  Google Scholar 

  • Wittmayer PK, McKenzie JL, Raines RT (1998) Degenerate DNA recognition by I-PpoI endonuclease. Gene 206:11–21

    Article  PubMed  CAS  Google Scholar 

  • Yokoyama E, Yamagishi K, Hara A (2002) Group-I intron containing a putative homing endonuclease gene in the small subunit ribosomal DNA of Beauveria bassiana IFO 31676. Mol Biol Evol 19:2022–2025

    PubMed  CAS  Google Scholar 

  • Zaug AJ, Grabowski PJ, Cech TR (1983) Autocatalytic cyclization of an excised intervening sequence RNA is a cleavage-ligation reaction. Nature 301:578–583

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physical Biosciences, Lawrence Berkeley National Laboratory, 1 Cyclotron Road Mail Stop 20A-355, Berkeley, California, 94720, USA

    Eric A. Galburt

  2. Molecular, Cell and Developmental Biology, Center for Molecular Biology of RNA, UC Santa Cruz, 1156 High Street, Santa Cruz, California, 95064, USA

    Melissa S. Jurica

Authors
  1. Eric A. Galburt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Melissa S. Jurica
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wadsworth Center/NYSDOH, Center for Medical Science, 150 New Scotland Ave, Albany, NY, 12208, USA

    Marlene Belfort  & Victoria Derbyshire  & 

  2. Dept. of Chemical Engineering, Princeton University, A417 Engineering Quadrangle, Princeton, NJ, 08544, USA

    David W. Wood

  3. Fred Hutchinson Cancer Research, Center Institute, 1100 Fairview Ave. N. Mailstop A3-023, Seattle, WA, 98109, USA

    Barry L. Stoddard

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Galburt, E.A., Jurica, M.S. (2005). His-Cys Box Homing Endonucleases. In: Belfort, M., Wood, D.W., Stoddard, B.L., Derbyshire, V. (eds) Homing Endonucleases and Inteins. Nucleic Acids and Molecular Biology, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29474-0_6

Download citation

Publish with us

Policies and ethics

Search

Navigation