Exonucleases

Paul G Mitsis, Praelux Inc., Lawrenceville, New Jersey, USA

Published online: April 2001

DOI: 10.1038/npg.els.0001035

Exonucleases are a widely distributed class of enzymes that hydrolyse nucleic acids from a free end. They are involved in replication, repair, recombination, and the proper maturation and degradation of DNA and RNA, making them essential for the proper expression and maintenance of the genome.

Keywords: exonuclease; hydrolase; DNAase; RNAase; recombination; replication; repair; RNA processing; processivity

Figure 1. SN2 mechanism of nucleophilic substitution used by most exonucleases.
Figure 2. Model of the proposed transition state at the active site of the 3¢–5¢ exonuclease of the Klenow fragment of Escherichia coli DNA polymerase I. The hydrogen bonds between the two divalent metals (ME2+) are indicated by dashed lines. From Beese and Stietz (1991), reprinted with permission of T. Steitz.
Figure 3. (a) A structural model of lambda exonuclease modelled with DNA substrate. Lambda exonuclease is shown as a space-filling model with each subunit of trimer a different colour. DNA is shown as a stick model with double-stranded DNA shown entering the enzyme and the single-stranded DNA product leaving. Coordinates provided by R. Kovall. (b) A structural model of exonuclease I modelled with single-stranded DNA substrate showing binding of DNA in deep cleft of enzyme. Exonuclease I is shown as a space-filling model; DNA is shown as a stick model. Protein loop proposed to cover DNA is not ordered in the crystal structure and not shown in this representation. Relative sizes of the two proteins are not to scale. Coordinates provided by W. Breyer.
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 References
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    Cowan J (1998) Metal activation of enzymes in nucleic acid biochemistry. Chemical Reviews 98: 1067–1087.
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    Spahr PF (1964) Purification and properties of ribonuclease II from Escherichia coli. Journal of Biological Chemistry 239: 3716.
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    Van Hoof A and Parker R (1999) The exosome: a proteosome for RNA? Cell 99: 347–350.
    Viswanathan M, Dower KW and Lovett ST (1998) Identification of a potent DNase activity associated with RNase T of Escherichia coli. Journal of Biological Chemistry 273: 35126–35131.
    Viswanathan M and Lovett ST (1998) Single-strand DNA-specific exonucleases in Escherichia coli: roles in repair and mutation avoidance. Genetics 149: 7–16.
    Viswanathan M and Lovett ST (1999) Exonuclease X of Escherichia coli: a novel 3¢–5¢ DNase and DnaQ superfamily member involved in DNA repair. Genetics 274: 30094–30100.
    Wang D and Hawley DK (1993) Identification of a 3¢–5¢ exonuclease activity associated with human RNA polymerase II. Proceedings of the National Academy of Sciences of the USA 90: 843–847.
 Further Reading
    Bernad A, Blanco L, Lazaro JM, Martin G and Salas M (1989) A conserved 3¢–5¢ exonuclease active site in prokaryotic and eukaryotic DNA polymerases. Cell 59: 219–228.
    Brody RS and Doherty KG (1985) Stereochemical course of hydrolysis of DNA by exonuclease I from Escherichia coli. Biochemistry 24: 2072–2076.
    Ceska TA and Sayers JR (1998) Structure-specific DNA cleavage by 5¢ nucleases. Trends in Biochemical Sciences 23: 331–336.
    Clark AJ (1973) Recombination deficient mutants of E. coli and other bacteria. Annual Review of Genetics 7: 67–86.
    Cowan J (1998) Metal activation of enzymes in nucleic acid biochemistry. Chemical Reviews 98: 1067–1087.
    Deutscher MP (1993) Ribonuclease multiplicity, diversity, and complexity. Journal of Biological Chemistry 268: 13011–13014.
    book Gerlt JA (1993) "Mechanistic principles of enzyme-catalyzed cleavage of phosphodiester bonds". In: Linn SM, Lloyd RS and Roberts RJ (eds) Nucleases, 2nd ed. pp. 1–34. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
    book Kornberg A and Baker TA (1992) DNA Replication, 2nd edn. New York: Freeman.
    Kowalczykowski SC (2000) Initiation of genetic recombination and recombination-dependent replication. Trends in Biological Chemistry 25: 156–165.
    book Linn SM and Roberts RJ (1982) Nucleases. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
    book Linn SM, Lloyd RS and Roberts RJ (1993) Nucleases, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
    Singer MF and Tolbert G (1964) Science 145: 593.
    Spahr PF (1964) Purification and properties of ribonuclease II from Escherichia coli. Journal of Biological Chemistry 239: 3716.
    Van Hoof A and Parker R (1999) The exosome: a proteosome for RNA? Cell 99: 347–350.
    Viswanathan M and Lovett ST (1998) Single-strand DNA-specific exonucleases in Escherichia coli: roles in repair and mutation avoidance. Genetics 149: 7–16.
    Viswanathan M, Dower KW and Lovett ST (1998) Identification of a potent DNase activity associated with RNase T of Escherichia coli. Journal of Biological Chemistry 273: 35126–35131.

Related Sub-Topics:

Replication and Recombination | RNA Structure and Function | DNA Structure and Function | DNA Damage and Repair | Enzymes: Structure and Action Mechanism | Nucleic Acids: Structure, Function, Metabolism
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Article Title: Exonucleases
 
How to Cite close
Mitsis, Paul G(Apr 2001) Exonucleases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001035]