Deoxyribonuclease IV

Deoxyribonuclease IV (phage-T4-induced) (, "endodeoxyribonuclease IV (phage T4-induced)", "E. coli endonuclease IV", "endodeoxyribonuclease", "redoxyendonuclease", "deoxriboendonuclease", "Escherichia coli endonuclease II", "endonuclease II", "DNA-adenine-transferase") is a kind of Endonuclease that catalyzes the degradation nucleotides in DsDNA by attacking the 5'-terminal end.
Deoxyribonuclease IV is a type of deoxyribonuclease that functions at abasic or apurinic-apyrimidininc sites when the cell is undergoing nucleotide excision repair pathway. In addition, the endonuclease IV consists of several activities such as AP endonuclease, 3'-diesterase, 3'->5' exonuclease, and 3'phosphatase.
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).
Discovery.
Deoxyribonuclease IV was first isolated from rabbit tissues in 1968, and its molecular weight was determined to be 42,000 dalton. It was discovered that this enzyme resembels several microbial endonuclease activities of DNA polymerase I found in Escherichia coli, which appear to be necessary for DNA repair and recombination.
Structure.
DNase IV is coomposed of 185 amino acid residues with magnesium ions acting as a cofactor. Diavalent metal ion such as Mg²⁺ which acting as cofactor during the cleavage of 5'-mononucleotides. 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.
Enzyme Activities in cell environment and DNA.
70% of the total DNase IV activitiy was found in the cytoplasm while 30% was found in cell nuclei. In human body, DNase IV was required for cleavage of a reaction intermediate generated by template strand displacement during gap-filling.
During the endonuclease activity, conformational change in DNA occurs in a way that exposes the abasic site by benting the DNA by 90 degrees, which inovles flipping out the sugar moiety into a small pocket that would not form watson-crick base pair.