MF_00148

Uracil-DNA glycosylase [ung]

HAMAP entry
Member databaseHAMAP
HAMAP typefamily
Short nameUDG

Description
Imported from IPR002043

Uracil-DNA glycosylase
3.2.2
(UDG, UNG)
[6]
is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. UDGs were classified into 4 families
[4, 3]
.

Family 1 enzymes are active against uracil in both ssDNA and dsDNA, and recognise uracil explicitly in an extrahelical conformation via a combination of protein and bound-water interactions
[3]
. Family 1 enzymes are present in Eubacteria, Eukarya and in some eukaryotic viruses. The sequence of uracil-DNA glycosylases is extremely well conserved
[2]
in bacteria and eukaryotes as well as in herpes viruses
[8]
. More distantly related uracil-DNA glycosylases are also found in poxviruses
[7]
. In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human nuclear UNG2 and mitochondrial UNG1are both encoded by the UNG gene
[5, 1]
. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localisation
[5]
. The catalytic C-terminal domains of UNGs are highly conserved at both the sequence and structure level while the N-terminal domains are diverse and are thought to be involved in subcellular localisation and protein-protein interactions
[8]
.

References
Imported from IPR002043

1.Uracil in DNA and its processing by different DNA glycosylases. Visnes T, Doseth B, Pettersen HS, Hagen L, Sousa MM, Akbari M, Otterlei M, Kavli B, Slupphaug G, Krokan HE. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 364, 563-8, (2009). View articlePMID: 19008197

2.Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. Olsen LC, Aasland R, Wittwer CU, Krokan HE, Helland DE. EMBO J. 8, 3121-5, (1989). View articlePMID: 2555154

3.Structure and function in the uracil-DNA glycosylase superfamily. Pearl LH. Mutat. Res. 460, 165-81, (2000). View articlePMID: 10946227

4.Recent progress in the biology, chemistry and structural biology of DNA glycosylases. Scharer OD, Jiricny J. Bioessays 23, 270-81, (2001). View articlePMID: 11223884

5.Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene. Slupphaug G, Markussen FH, Olsen LC, Aasland R, Aarsaether N, Bakke O, Krokan HE, Helland DE. Nucleic Acids Res. 21, 2579-84, (1993). View articlePMID: 8332455

6.DNA repair enzymes. Sancar A, Sancar GB. Annu. Rev. Biochem. 57, 29-67, (1988). View articlePMID: 3052275

7.Identification of a poxvirus gene encoding a uracil DNA glycosylase. Upton C, Stuart DT, McFadden G. Proc. Natl. Acad. Sci. U.S.A. 90, 4518-22, (1993). View articlePMID: 8389453

8.A structurally conserved motif in γ-herpesvirus uracil-DNA glycosylases elicits duplex nucleotide-flipping. Earl C, Bagneris C, Zeman K, Cole A, Barrett T, Savva R. Nucleic Acids Res. 46, 4286-4300, (2018). PMID: 29596604

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