uracil-DNA glycosylases (UDG) and related enzymes; Uracil-DNA glycosylases (UDGs) initiate repair of uracils in DNA. Uracil may arise from misincorporation of dUMP residues by DNA polymerase or via deamination of cytosine. Uracil in DNA mispaired with guanine is one of the major pro-mutagenic events, causing G:C->A:T mutations; thus, UDG is an essential enzyme for maintaining the integrity of genetic information. UDGs have been classified into various families on the basis of their substrate specificity, conserved motifs, and structural similarities. Although these families demonstrate different substrate specificities, often the function of one enzyme can be complemented by the other. UDG family 1 is the most efficient uracil-DNA glycosylase (UDG, also known as UNG) and shows a specificity for uracil in DNA. UDG family 2 includes thymine DNA glycosylase which removes uracil and thymine from G:U and G:T mismatches, and mismatch-specific uracil DNA glycosylase (MUG) which in Escherichia coli is highly specific to G:U mismatches, but also repairs G:T mismatches at high enzyme concentration. UDG family 3 includes Human SMUG1 which can remove uracil and its oxidized pyrimidine derivatives from, single-stranded DNA and double-stranded DNA with a preference for single-stranded DNA. Pedobacter heparinus SMUG2, which is UDG family 3 SMUG1-like, displays catalytic activities towards DNA containing uracil or hypoxanthine/xanthine. UDG family 4 includes Thermotoga maritima TTUDGA, a robust UDG which like family 1, acts on double-stranded and single-stranded uracil-containing DNA. UDG family 5 (UDGb) includes Thermus thermophilus HB8 TTUDGB which acts on double-stranded uracil-containing DNA; it is a hypoxanthine DNA glycosylase acting on double-stranded hypoxanthine-containing DNA except for the C/I base pair, as well as a xanthine DNA glycosylase which acts on both double-stranded and single-stranded xanthine-containing DNA. UDG family 6 hypoxanthine-DNA glycosylase lacks any detectable UDG activity; it excises hypoxanthine. Other UDG families include one represented by Bradyrhizobium diazoefficiens Blr0248 which prefers single-stranded DNA and removes uracil, 5-hydroxymethyl-uracil or xanthine from it.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344925877  29 ESFLEEELRLNAELSQLQFSEPVGIIYNPVEYAWEPHRNYVTRYCQGPKEVLFLGMNPGPFGMAQTGVPFGEVSMVRDWL 108
Cdd:cd19374    1 EKLLEIARRLSEELDALRFSEPVAHVYNPLEYAWEPHEAYLRRYGNGGKKVLFLGMNPGPWGMAQTGVPFGEVAAVRDWL 80

                         90       100
                 ....*....|....*....|....*..
gi 344925877 109 GIVGPVLTPPQEHPKRPVLGLECPQSE 135
Cdd:cd19374   81 GIEGPVGKPEKEHPKRPVEGFECPRSE 107

Uracil DNA glycosylase family 3 subfamily, includes single-strand-selective monofunctional uracil-DNA glycosylase 1 and similar proteins; Uracil DNA glycosylase family 3 includes Human SMUG1 that can remove uracil and its oxidized pyrimidine derivatives from both, single-stranded DNA and double-stranded DNA, with a preference for single-stranded DNA substrates. The SMUG-targeted mismatched uracil derivatives include 5-hydroxyuracil, 5-hydroxymethyluracil and 5-formyluracil. Also included in this subfamily is Geobacter metallireducens SMUG1 which has dual substrate specificities for DNA with uracil or xanthine. UDG catalyzes the removal of uracil from DNA to initiate the DNA base excision repair pathway. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. Uracil mispaired with guanine in DNA is one of the major pro-mutagenic events, causing G:C->A:T mutations. Thus, UDG is an essential enzyme for maintaining the integrity of genetic information. UDGs have been classified into various families on the basis of their substrate specificity, conserved motifs, and structural similarities. Although these families demonstrate different substrate specificities, often the function of one enzyme can be complemented by the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344925877  29 ESFLEEELRLNAELSQLQFSEPVGIIYNPVEYAWEPHRNYVTRYCQGPKEVLFLGMNPGPFGMAQTGVPFGEVSMVRDWL 108
Cdd:cd19374    1 EKLLEIARRLSEELDALRFSEPVAHVYNPLEYAWEPHEAYLRRYGNGGKKVLFLGMNPGPWGMAQTGVPFGEVAAVRDWL 80

                         90       100
                 ....*....|....*....|....*..
gi 344925877 109 GIVGPVLTPPQEHPKRPVLGLECPQSE 135
Cdd:cd19374   81 GIEGPVGKPEKEHPKRPVEGFECPRSE 107

Uracil DNA glycosylase family 3 subfamily, includes single-strand-selective monofunctional uracil-DNA glycosylase 1 and similar proteins; Uracil DNA glycosylase family 3 includes Human SMUG1 that can remove uracil and its oxidized pyrimidine derivatives from both, single-stranded DNA and double-stranded DNA, with a preference for single-stranded DNA substrates. The SMUG-targeted mismatched uracil derivatives include 5-hydroxyuracil, 5-hydroxymethyluracil and 5-formyluracil. Also included in this subfamily is Geobacter metallireducens SMUG1 which has dual substrate specificities for DNA with uracil or xanthine. UDG catalyzes the removal of uracil from DNA to initiate the DNA base excision repair pathway. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. Uracil mispaired with guanine in DNA is one of the major pro-mutagenic events, causing G:C->A:T mutations. Thus, UDG is an essential enzyme for maintaining the integrity of genetic information. UDGs have been classified into various families on the basis of their substrate specificity, conserved motifs, and structural similarities. Although these families demonstrate different substrate specificities, often the function of one enzyme can be complemented by the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 344925877  29 ESFLEEELRLNAELSQLQFSEPVGIIYNPVEYAWEPHRNYVTRYCQGPKEVLFLGMNPGPFGMAQTGVPFGEVSMVRDWL 108
Cdd:cd19374    1 EKLLEIARRLSEELDALRFSEPVAHVYNPLEYAWEPHEAYLRRYGNGGKKVLFLGMNPGPWGMAQTGVPFGEVAAVRDWL 80

                         90       100
                 ....*....|....*....|....*..
gi 344925877 109 GIVGPVLTPPQEHPKRPVLGLECPQSE 135
Cdd:cd19374   81 GIEGPVGKPEKEHPKRPVEGFECPRSE 107

Uracil DNA glycosylase family 3-like subfamily, includes single-strand-selective monofunctional uracil-DNA glycosylase 2 and similar proteins; Uracil DNA glycosylase family 3-like, which includes Pedobacter heparinus SMUG2, displays catalytic activities towards DNA containing uracil or hypoxanthine/xanthine. UDG catalyzes the removal of uracil from DNA to initiate the DNA base excision repair pathway. Uracil in DNA can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Uracil mispaired with guanine in DNA is one of the major pro-mutagenic events, causing G:C->A:T mutations. Thus, UDG is an essential enzyme for maintaining the integrity of genetic information. UDGs have been classified into various families on the basis of their substrate specificity, conserved motifs, and structural similarities. Although these families demonstrate different substrate specificities, often the function of one enzyme can be complemented by the other.

                         10        20
                 ....*....|....*....|..
gi 344925877  77 KEVLFLGMNPGPFGMAQTGVPF 98
Cdd:cd19375   50 KRVLILGINPGRFGAGVTGIPF 71