Biology:Deoxyribonuclease IV

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Deoxyribonuclease IV (phage-T4-induced)
Identifiers
EC number3.1.21.2
CAS number63363-78-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

Deoxyribonuclease IV (phage-T4-induced) (EC 3.1.21.2, endodeoxyribonuclease IV (phage T4-induced), E. coli endonuclease IV, endodeoxyribonuclease, redoxyendonuclease, deoxriboendonuclease, Escherichia coli endonuclease II, endonuclease II, DNA-adenine-transferase) is catalyzes the degradation nucleotides[1] in DsDNA by attacking the 5'-terminal end.[2][3][4]

Deoxyribonuclease IV is a type of deoxyribonuclease that has both an exonucleolytic and an endonucleolytic activity.[1] It functions at abasic or apurinic-apyrimidininc sites when the cell is undergoing nucleotide excision repair pathway.[5] In addition, the endonuclease IV consists of several activities such as AP endonuclease, 3'-diesterase, 3'->5' exonuclease, and 3'phosphatase.[6]

The endonuclease IV is encoded by denB of bacteriophage T4 and its binding sequence is 5′-dT||dCdAdCdTdTdC-3′. It has been discovered that serine 176 residue plays a crucial role in increasing the hydrolysis rate of the endonuclease of a consensus sequence containing cytidine. The endonuclease IV falls under a structurally resembling members with apyrimidininc endonuclease I (APE1).[7]

Discovery

Deoxyribonuclease IV was first isolated from rabbit tissues in 1968. Specifically, it was found in rabbit bone marrow by Lindahl.[8] And its molecular weight was determined to be 42,000 dalton. It was discovered that this enzyme resembles several microbial endonuclease activities of DNA polymerase I found in Escherichia coli, which appear to be necessary for DNA repair and recombination.[9] It also resembles gamma exonuclease, which performs an important function in recombination of bacteriophage.[10]

Structure

DNase IV is composed of 185 amino acid residues with magnesium ions acting as a cofactor. Divalent metal ions such as Mg²⁺ act as cofactor during the cleavage of 5'-mononucleotides.[11] DNase IV prefers to attack native DNA acting as an endonuclease with metal ions either Mg++ or Mn++.[12] Its TIM beta barrel core surrounded by helices with three metal ions —either three Zn2+ or two Zn2+ and one Mn2+ which plays crucial role in AP excision repair.[13]

Function

DNase IV attacks dsDNA at 5' ends by liberating 5' mononucleotides but it does not attack any monomers in polydeoxyribonucleotides in a random fashion. It cleaves polydeoxyribonucleotides in an exonucleolytic fashion from 5' end, meaning it removes a nucleotide chain that is adjacent to the 5' terminal end rather than cleaving a nucleotide located in the middle of the chain. DNase IV works by attacking multiple polynucleotide chains at the same time.[10] Since it does not cleave dsDNA in a processive way, the rate of hydrolysis of this enzyme is faster than native DNA in terms of kinetics.[14] DNase IV does not recognize specific sequences on DNA for non-staggered cleavage. However, it requires two base pairs at one cleavage site, and the other cleavage site of double-stranded DNA should have more than 10 base pairs.[12]

Enzyme Activities in cell environment and DNA

70% of the total DNase IV activity was found in the cytoplasm while 30% was found in cell nuclei.[1] In human body, DNase IV was required for cleavage of a reaction intermediate generated by template strand displacement during gap-filling.[15]

During the endonuclease activity, conformational change in DNA occurs in a way that exposes the abasic site by bending the DNA by 90 degrees, which involves flipping out the sugar moiety into a small pocket that would not form watson-crick base pair.[13]

DNase IV acts on double stranded DNA in repair by breaking phosphodiester bonds, but the number of cleavages by this enzyme is smaller than the extent of polymerization of DNA.[14]

Difference between DNase III vs. DNase IV

In crude cell extracts from lymphoid organs, DNase III and DNase IV show major activities because DNase I activity is inhibited. The activities of DNase III and DNase IV depend on two Mg++ as cofactors and these enzymes are localized in cell nuclei. Even though they require same divalent metal to function, there are major difference in liberating polynucleotides. DNase III cleaves a single strand of DNA from 3' terminal end but DNase IV cleaves a double strand of DNA from 5' terminal end.[10] Because DNase III degrades single stranded DNA, the rate of hydrolysis of DNase III is more rapid than that of DNase IV.[1]

See also

  • Phage T4

References

  1. ↑ 1.0 1.1 1.2 1.3 "Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I". The Journal of Biological Chemistry 269 (46): 28535–28538. November 1994. doi:10.1016/s0021-9258(19)61935-6. PMID 7961795. 
  2. ↑ "Endonuclease II of E. coli. I. Isolation and purification". Proceedings of the National Academy of Sciences of the United States of America 62 (3): 934–940. March 1969. doi:10.1073/pnas.62.3.934. PMID 4895219. Bibcode: 1969PNAS...62..934F. 
  3. ↑ "Endonuclease II of Escherichia coli. Degradation of partially depurinated deoxyribonucleic acid". Biochemistry 10 (26): 4986–4993. December 1971. doi:10.1021/bi00802a024. PMID 4944066. 
  4. ↑ "Enzymatic breakage of deoxyribonucleic acid. I. Purification and properties of endonuclease II from T4 phage-infected Escherichia coli". The Journal of Biological Chemistry 244 (22): 6182–6191. November 1969. doi:10.1016/S0021-9258(18)63523-9. PMID 4310836. 
  5. ↑ "Endonuclease II of Escherichia coli. II. Enzyme properties and studies on the degradation of alkylated and native deoxyribonucleic acid". The Journal of Biological Chemistry 244 (21): 5879–5889. November 1969. doi:10.1016/S0021-9258(18)63556-2. PMID 4981786. 
  6. ↑ "Characterization of an endonuclease IV 3'-5' exonuclease activity". The Journal of Biological Chemistry 278 (5): 3048–3054. January 2003. doi:10.1074/jbc.m210750200. PMID 12444080. 
  7. ↑ "The Ser176 of T4 endonuclease IV is crucial for the restricted and polarized dC-specific cleavage of single-stranded DNA implicated in restriction of dC-containing DNA in host Escherichia coli". Nucleic Acids Research 35 (20): 6692–6700. 2007-11-29. doi:10.1093/nar/gkm722. PMID 17913749. 
  8. ↑ Grondal-Zocchi, G.; Verly, W. G. (1985-01-15). "Deoxyribonuclease IV from rat liver chromatin and the excision of apurinic sites from depurinated DNA". The Biochemical Journal 225 (2): 535–542. doi:10.1042/bj2250535. ISSN 0264-6021. PMID 3977844. 
  9. ↑ "Deoxyribonuclease IV: a new exonuclease from mammalian tissues". Proceedings of the National Academy of Sciences of the United States of America 62 (2): 597–603. February 1969. doi:10.1073/pnas.62.2.597. PMID 5256235. Bibcode: 1969PNAS...62..597L. 
  10. ↑ 10.0 10.1 10.2 "Deoxyribonuclease IV: a new exonuclease from mammalian tissues". Proceedings of the National Academy of Sciences of the United States of America 62 (2): 597–603. February 1969. doi:10.1073/pnas.62.2.597. PMID 5256235. 
  11. ↑ (in English) Molecular biology of nucleases. Boca Raton: CRC Press. 1995. ISBN 978-0-8493-7658-0. OCLC 31436640. https://www.worldcat.org/oclc/31436640. 
  12. ↑ 12.0 12.1 Campbell, Aine M.; Winder, Frank G. (August 1983). "Properties of deoxyribonuclease 4 from Aspergillus nidulans" (in en). Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 746 (3): 125–132. doi:10.1016/0167-4838(83)90065-1. PMID 6349692. https://linkinghub.elsevier.com/retrieve/pii/0167483883900651. 
  13. ↑ 13.0 13.1 "The cutting edges in DNA repair, licensing, and fidelity: DNA and RNA repair nucleases sculpt DNA to measure twice, cut once". DNA Repair 19: 95–107. July 2014. doi:10.1016/j.dnarep.2014.03.022. PMID 24754999. 
  14. ↑ 14.0 14.1 Lindahl, Tomas (February 1971). "The Action Pattern of Mammalian Deoxyribonuclease IV" (in en). European Journal of Biochemistry 18 (3): 415–421. doi:10.1111/j.1432-1033.1971.tb01258.x. ISSN 0014-2956. PMID 5100828. https://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1971.tb01258.x. 
  15. ↑ "Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1)". The EMBO Journal 16 (11): 3341–3348. June 1997. doi:10.1093/emboj/16.11.3341. PMID 9214649. 

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