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Information on EC 3.2.2.28 - double-stranded uracil-DNA glycosylase and Organism(s) Escherichia coli and UniProt Accession P0A9H1
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3.2.2.28 double-stranded uracil-DNA glycosylaseIUBMB Comments
No activity on DNA containing a T/G mispair or single-stranded DNA containing either a site-specific uracil or 3,N4-ethenocytosine residue , significant role for double-stranded uracil-DNA glycosylase in mutation avoidance in non-dividing E. coli . Uracil-DNA glycosylases are widespread enzymes that are found in all living organisms. Uracil-DNA glycosylase (EC 3.2.2.27) and EC 3.2.2.28 form a central part of the DNA-repair machinery since they initiate the DNA base-excision repair pathway by hydrolysing the N-glycosidic bond between uracil and the deoxyribose sugar thereby catalysing the removal of mis-incorporated uracil from DNA.
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Word Map
- 3.2.2.28
- thymine
- mispairs
- guanine
-
deamination
- cytosine
-
thymine-dna
- glycosylases
- pyrimidine
-
etheno
- purine
- 3,n4-ethenocytosine
-
thermus
- adducts
- thermophilus
-
single-stranded
- dutp
-
exocyclic
- n2,3-ethenoguanine
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Specifically hydrolyses mismatched double-stranded DNA and polynucleotides, releasing free uracil
Synonyms
double-strand uracil-dna glycosylase, dsudg, double-stranded uracil-dna glycosylase, g:t/u mismatch-specific dna glycosylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
uracil-double-stranded DNA deoxyribohydrolase (uracil-releasing)
No activity on DNA containing a T/G mispair or single-stranded DNA containing either a site-specific uracil or 3,N4-ethenocytosine residue [2], significant role for double-stranded uracil-DNA glycosylase in mutation avoidance in non-dividing E. coli [3]. Uracil-DNA glycosylases are widespread enzymes that are found in all living organisms. Uracil-DNA glycosylase (EC 3.2.2.27) and EC 3.2.2.28 form a central part of the DNA-repair machinery since they initiate the DNA base-excision repair pathway by hydrolysing the N-glycosidic bond between uracil and the deoxyribose sugar thereby catalysing the removal of mis-incorporated uracil from DNA.
CAS REGISTRY NUMBER
COMMENTARY
59088-21-0
cf. EC 3.2.2.27
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3,N4-ethenocytosine-containing single-stranded DNA + H2O
3,N4-ethenocytosine + single-stranded DNA with abasic site
the enzyme excised both 3,N4-ethenocytosine and uracil from DNA. 3,N4-ethenocytosine is significantly better as a substrate in terms of binding and hydrolysis. The tighter binding of the 3,N4-ethenocytosine containing substrate by MUG probably also accounts for its activity against single-stranded DNA containing 3,N4-ethenocytosine. Cleavage of the single-stranded substrate is 1500fold slower than the double-stranded substrate
-
-
?
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
-
-
-
?
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
the enzyme excised both 3,N4-ethenocytosine and uracil from DNA. 3,N4-ethenocytosine is significantly better as a substrate in terms of binding and hydrolysis. The tighter binding of the 3,N4-ethenocytosine containing substrate by MUG probably also accounts for its activity against single-stranded DNA containing 3,N4-ethenocytosine. Cleavage of the single-stranded substrate is 1500fold slower than the double-stranded substrate. Of the different substrates tested, a duplex containing the 3,N4-ethenocytosine pair has the highest affinity for the enzyme, U/G is the next best substrate
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-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
dsUDG can remove uracil from G/U mispairs
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-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
the enzyme activity against the uracil-containing single-stranded DNA is so low that it is not likely to be of any significance. Of the different substrates tested, a duplex containing the 3,N4-ethenocytosine pair has the highest affinity for the enzyme, U/G is the next best substrate
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-
?
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
-
3,N4-ethenocytosine is recognized and efficiently excised from the 3,N4-ethenocytosine/G mismatch
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-
?
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
-
Dug is active on duplex oligonucleotides (34-mers) that contain site-specific 3,N4-ethenocytosine/G, and 3,N4-ethenocytosine/A mismatches
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-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
-
Dug is active on duplex oligonucleotides (34-mers) that contain site-specific U/G or U/A mismatches. Dug excises a near stoichiometric amount of uracil from U/G-containing oligonucleotide substrate. The lack of turnover is the result of strong binding by Dug to the reaction product apyrimidinic-site
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-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
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excision of uracil from U/G mismatch
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-
?
additional information
?
-
Mug is expressed poorly in exponentially growing cells and has no apparent role in mutation avoidance in these cells. Mug is fairly abundant in stationary-phase cells and has an important anti-mutator role at this stage of cell growth
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-
?
additional information
?
-
5-Hydroxyuracil and inosine (hypoxanthine) show cleavage rates 23 orders of magnitude slower than 3,N4-ethenocytosine. Thymine, 5-hydroxymethyluracil, and 5-hydroxycytosine are cleaved to some extent, although extremely slowly
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-
?
additional information
?
-
inactive on single-stranded oligo(U)
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-
?
additional information
?
-
-
activity is not detected on DNA containing a T/G mispair or single-stranded DNA containing either a site-specific uracil or 3,N4-ethenocytosine residue. Endonuclease IV stimulates Dug activity by enhancing the rate and extent of uracil excision by promoting dissociation of Dug from the apyrimidinic-site/G-containing 34-mer. Catalytically active endonuclease IV is required to mediate Dug turnover
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-
?
additional information
?
-
-
the excision of thymine in a G/T mismatch by dsUDG is extremely low. This enzymatic activity does not have a real biological significance
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
Mug is expressed poorly in exponentially growing cells and has no apparent role in mutation avoidance in these cells. Mug is fairly abundant in stationary-phase cells and has an important anti-mutator role at this stage of cell growth
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
double-strand uracil-DNA glycosylase is insensitive to uracil-DNA glycosylase inhibitor protein, i.e. Ugi
-
additional information
-
double-strand uracil-DNA glycosylase is insensitive to uracil-DNA glycosylase inhibitor protein, i.e. Ugi
-
additional information
-
double-strand uracil-DNA glycosylase is insensitive to uracil-DNA glycosylase inhibitor protein, i.e. Ugi
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
endonuclease IV
-
endonuclease IV stimulates Dug activity by enhancing the rate and extent of uracil excision by promoting dissociation of Dug from the apyrimidinic-site/G-containing 34-mer. Catalytically active endonuclease IV is required to mediate Dug turnover
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
poorly expressed in exponentially growing cells. Mug is overexpressed as cells enter stationary phase, and it is maintained at a fairly high level in resting cells. This is true of cells grown in rich or minimal media, and the principal regulation of mug is at the level of mRNA. Although the expression of mug is strongly dependent on the stationary-phase sigma factor, when cells are grown in minimal media, it shows only a modest dependence on stationary-phase sigma factor when cells are grown in rich media
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine
crystal structures of the mismatch-specific uracil DNA-glycosylase from Escherichia coli, and of a DNA complex, reveal a remarkable structural and functional homology to UDGs despite low sequence identity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sung, J.S.
Mosbaugh, D.W.: Escherichia coli double-strand uracil-DNA glycosylase: involvement in uracil-mediated DNA base excision repair and stimulation of activity by endonuclease IV
Biochemistry
39
10224-10235
2000
Escherichia coli
Barrett, T.E.; Savva, R.; Panayotou, G.; Barlow, T.; Brown, T.; Jiricny, J.; Pearl, LH.
Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions.
Cell
92
117-129
1998
Escherichia coli (P0A9H1), Escherichia coli
Barrett, T.E.; Schrer, O.D.; Savva, R.; Brown, T.; Jiricny, J.; Verdine, G.L.; Pearl, L.H.
Crystal structure of a thwarted mismatch glycosylase DNA repair complex
EMBO J.
18
6599-6609
1999
Escherichia coli (P0A9H1)
O'Neill, R.J.; Vorobeva, O.V.; Shahbakhti, H.; Zmuda, E.; Bhagwat, A.S.; Baldwin, G.S.
Mismatch uracil glycosylase from Escherichia coli: a general mismatch or a specific DNA glycosylase?
J. Biol. Chem.
278
20526-20532
2003
Escherichia coli (P0A9H1)
Mokkapati, S.K.; Fernandez de Henestrosa, A.R.; Bhagwat, A.S.
Escherichia coli DNA glycosylase Mug: a growth-regulated enzyme required for mutation avoidance in stationary-phase cells
Mol. Microbiol.
41
1101-1111
2001
Escherichia coli (P0A9H1)
Gallinari, P.; Jiricny, J.
A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase
Nature
383
735-738
1996
Escherichia coli (P0A9H1), Escherichia coli
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