The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Laurence H Pearl - One of the best experts on this subject based on the ideXlab platform.
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structure and function in the uracil dna Glycosylase superfamily
Mutation Research-dna Repair, 2000Co-Authors: Laurence H PearlAbstract:Abstract Deamination of cytosine to uracil is one of the major pro-mutagenic events in DNA, causing G:C→A:T transition mutations if not repaired before replication. Repair of Uracil-DNA is achieved in a base-excision pathway initiated by a Uracil-DNA Glycosylase (UDG) enzyme of which four families have so far been identified. Family-1 enzymes are active against uracil in ssDNA and dsDNA, and recognise uracil explicitly in an extrahelical conformation via a combination of protein and bound-water interactions. Extrahelical recognition requires an efficient process of substrate location by ‘base-sampling’ probably by hopping or gliding along the DNA. Family-2 enzymes are mismatch specific and explicitly recognise the widowed guanine on the complementary strand rather than the extrahelical scissile pyrimidine. This allows a broader specificity so that some Family-2 enzymes can excise uracil and 3,N4-ethenocytosine from mismatches with guanine. Although structures are not yet available for Family-3 (SMUG) and Family-4 enzymes, sequence analysis suggests similar overall folds, and identifies common active site motifs but with a surprising lack of conservation of catalytic residues between members of the super-family.
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Uracil-DNA Glycosylase activities in hyperthermophilic micro-organisms
Fems Microbiology Letters, 1996Co-Authors: A Koulis, Laurence H Pearl, Don A. Cowan, Renos SavvaAbstract:Hyperthermophiles exist in conditions which present an increased threat to the informational integrity of their DNA, particularly by hydrolytic damage. As in mesophilic organisms, specific activities must exist to restore and protect this template function of DNA. In this study we have demonstrated the presence of thermally stable Uracil-DNA Glycosylase activities in seven hyperthermophiles; one bacterial: Thermotoga maritima, and six archaeal: Sulfolobus solfataricus, Sulfolobus shibatae, Sulfolobus acidocaldarius, Thermococcus litoralis, Pyrococcus furiosus and Pyrobaculum islandicum. Uracil-DNA Glycosylase inhibitor protein of the Bacillus subtilis bacteriophage PBS1 shows activity against all of these, suggesting a highly conserved tertiary structure between hyperthermophilic and mesophilic Uracil-DNA Glycosylases.
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Uracil‐DNA Glycosylase activities in hyperthermophilic micro‐organisms
Fems Microbiology Letters, 1996Co-Authors: A Koulis, Laurence H Pearl, Don A. Cowan, Renos SavvaAbstract:Hyperthermophiles exist in conditions which present an increased threat to the informational integrity of their DNA, particularly by hydrolytic damage. As in mesophilic organisms, specific activities must exist to restore and protect this template function of DNA. In this study we have demonstrated the presence of thermally stable Uracil-DNA Glycosylase activities in seven hyperthermophiles; one bacterial: Thermotoga maritima, and six archaeal: Sulfolobus solfataricus, Sulfolobus shibatae, Sulfolobus acidocaldarius, Thermococcus litoralis, Pyrococcus furiosus and Pyrobaculum islandicum. Uracil-DNA Glycosylase inhibitor protein of the Bacillus subtilis bacteriophage PBS1 shows activity against all of these, suggesting a highly conserved tertiary structure between hyperthermophilic and mesophilic Uracil-DNA Glycosylases.
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the structural basis of specific base excision repair by uracil dna Glycosylase
Nature, 1996Co-Authors: Renos Savva, Katherine E Mcauleyhecht, Tom Brown, Laurence H PearlAbstract:The 1.75-A crystal structure of the Uracil-DNA Glycosylase from herpes simplex virus type-1 reveals a new fold, distantly related to dinucleotide-binding proteins. Complexes with a trideoxynucleotide, and with uracil, define the DNA-binding site and allow a detailed understanding of the exquisitely specific recognition of uracil in DNA. The overall structure suggests binding models for elongated single- and double-stranded DNA substrates. Conserved residues close to the uracil-binding site suggest a catalytic mechanism for hydrolytic base excision.
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Cloning and expression of the Uracil-DNA Glycosylase inhibitor (UGI) from bacteriophage PBS-1 and crystallization of a Uracil-DNA Glycosylase-UGI complex.
Proteins, 1995Co-Authors: Renos Savva, Laurence H PearlAbstract:The Uracil-DNA Glycosylase inhibitory protein (UGI) from the bacterio-phage PBS-l has been cloned and overexpressed. The nucleotide sequence is identical to that for the previously described PBS-2 inhibitor. The recombinant PBS-l UGI inhibits the Uracil-DNA Glycosylase from herpes simplex virus type-l (HSV-l UDGase), and a complex between the HSV-l UDGase and PBS-l UGI has been crystallized. The crystals have unit cell dimensions a = 143.21 A, c = 40.78 A and are in a polar hexagonal space group. There is a single complex in the asymmetric unit with a solvent content of 62% by volume and the crystals diffract to 2.5A on a synchrotron radiation source. © 1995 Wiley-Liss, Inc.
Renos Savva - One of the best experts on this subject based on the ideXlab platform.
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Uracil-DNA Glycosylase activities in hyperthermophilic micro-organisms
Fems Microbiology Letters, 1996Co-Authors: A Koulis, Laurence H Pearl, Don A. Cowan, Renos SavvaAbstract:Hyperthermophiles exist in conditions which present an increased threat to the informational integrity of their DNA, particularly by hydrolytic damage. As in mesophilic organisms, specific activities must exist to restore and protect this template function of DNA. In this study we have demonstrated the presence of thermally stable Uracil-DNA Glycosylase activities in seven hyperthermophiles; one bacterial: Thermotoga maritima, and six archaeal: Sulfolobus solfataricus, Sulfolobus shibatae, Sulfolobus acidocaldarius, Thermococcus litoralis, Pyrococcus furiosus and Pyrobaculum islandicum. Uracil-DNA Glycosylase inhibitor protein of the Bacillus subtilis bacteriophage PBS1 shows activity against all of these, suggesting a highly conserved tertiary structure between hyperthermophilic and mesophilic Uracil-DNA Glycosylases.
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Uracil‐DNA Glycosylase activities in hyperthermophilic micro‐organisms
Fems Microbiology Letters, 1996Co-Authors: A Koulis, Laurence H Pearl, Don A. Cowan, Renos SavvaAbstract:Hyperthermophiles exist in conditions which present an increased threat to the informational integrity of their DNA, particularly by hydrolytic damage. As in mesophilic organisms, specific activities must exist to restore and protect this template function of DNA. In this study we have demonstrated the presence of thermally stable Uracil-DNA Glycosylase activities in seven hyperthermophiles; one bacterial: Thermotoga maritima, and six archaeal: Sulfolobus solfataricus, Sulfolobus shibatae, Sulfolobus acidocaldarius, Thermococcus litoralis, Pyrococcus furiosus and Pyrobaculum islandicum. Uracil-DNA Glycosylase inhibitor protein of the Bacillus subtilis bacteriophage PBS1 shows activity against all of these, suggesting a highly conserved tertiary structure between hyperthermophilic and mesophilic Uracil-DNA Glycosylases.
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the structural basis of specific base excision repair by uracil dna Glycosylase
Nature, 1996Co-Authors: Renos Savva, Katherine E Mcauleyhecht, Tom Brown, Laurence H PearlAbstract:The 1.75-A crystal structure of the Uracil-DNA Glycosylase from herpes simplex virus type-1 reveals a new fold, distantly related to dinucleotide-binding proteins. Complexes with a trideoxynucleotide, and with uracil, define the DNA-binding site and allow a detailed understanding of the exquisitely specific recognition of uracil in DNA. The overall structure suggests binding models for elongated single- and double-stranded DNA substrates. Conserved residues close to the uracil-binding site suggest a catalytic mechanism for hydrolytic base excision.
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Structural studies of a Uracil-DNA Glycosylase from herpes simplex virus type 1
1995Co-Authors: Renos SavvaAbstract:The work presented in this thesis describes experiments carried out in order to determine the three-dimensional structure of a DNA repair enzyme, Uracil-DNA Glycosylase. An open reading frame, UL2, in the herpes simplex virus type 1 genome, is known to encode a Uracil-DNA Glycosylase. By sequence homology, there are three candidate start codons which might express a functional Uracil-DNA Glycosylase. Expression from two of these was attempted in Escherichia coli, using plasmids designed for high level production of recombinant proteins. The second candidate start codon produces high levels of a soluble, functional Uracil-DNA Glycosylase in Escherichia coli both in a native form, and as part of a fusion protein. Both the fusion and the native form of the enzyme have been purified to apparent homogeneity, as has a recombinantly expressed insoluble Escherichia coli Uracil-DNA Glycosylase. Preliminary attempts were made at deriving structural and functional information from the soluble, native recombinant herpes simplex enzyme with the use of circular dichroism. This form of Uracil-DNA Glycosylase has subsequently been crystallised in two ways, firstly as the free enzyme, and secondly in a complex with a single stranded DNA oligonucleotide. Extensive optimisation of the crystallisation parameters have been carried out in conjunction with modifications to the original purification protocol, and large, single crystals of both free, and DNA bound forms, suitable for X-ray diffraction studies are now readily reproduced. A systematic search for isomorphous heavy atom derivatives has been carried out for both types of crystal, and preliminary phases have been obtained for the DNA-bound form of the enzyme. This has enabled the calculation of an electron density map in which protein secondary structure features can be located. Improvement of this map will reveal the molecular structure of the enzyme/ DNA complex.
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Cloning and expression of the Uracil-DNA Glycosylase inhibitor (UGI) from bacteriophage PBS-1 and crystallization of a Uracil-DNA Glycosylase-UGI complex.
Proteins, 1995Co-Authors: Renos Savva, Laurence H PearlAbstract:The Uracil-DNA Glycosylase inhibitory protein (UGI) from the bacterio-phage PBS-l has been cloned and overexpressed. The nucleotide sequence is identical to that for the previously described PBS-2 inhibitor. The recombinant PBS-l UGI inhibits the Uracil-DNA Glycosylase from herpes simplex virus type-l (HSV-l UDGase), and a complex between the HSV-l UDGase and PBS-l UGI has been crystallized. The crystals have unit cell dimensions a = 143.21 A, c = 40.78 A and are in a polar hexagonal space group. There is a single complex in the asymmetric unit with a solvent content of 62% by volume and the crystals diffract to 2.5A on a synchrotron radiation source. © 1995 Wiley-Liss, Inc.
Hans E. Krokan - One of the best experts on this subject based on the ideXlab platform.
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human uracil dna Glycosylase deficiency associated with profoundly impaired immunoglobulin class switch recombination
Nature Immunology, 2003Co-Authors: Kohsuke Imai, Geir Slupphaug, Nadia Catalan, Monique Forveille, Bodil Kavli, Hans D. Ochs, Hans E. Krokan, Shigeaki Nonoyama, Patrick Revy, Alain FischerAbstract:Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil–DNA Glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.
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Human Uracil-DNA Glycosylase
Advances in DNA Damage and Repair, 1999Co-Authors: Hans E. Krokan, Sangeeta Bharati, Kristin Solum Steinsbekk, Hilde Nilsen, Camilla Skjelbred, Bodil Kavli, Frank Skorpen, Marit Otterlei, Rune Standal, Geir SlupphaugAbstract:Uracil in DNA results from either misincorporation of dUMP residues during replication, or from deamination of cytosine residues. The latter process results in premutagenic U:G mispairs that, unless uracil is removed, will cause GC→AT transitions in the subsequent round of replication. The 13.8 kb gene for human Uracil-DNA Glycosylase, UNG, is highly conserved and comprises 7 exons. It encodes more than 98% of the total Uracil-DNA Glycosylase activity in the cell. The crystal structure of the catalytic domain of UNG in complex with target DNA has demonstrated that all essential contacts are with the uracil-containing strand. The structure also reveals the mechanism of enzyme-assisted flipping of the uracil-containing nucleotide into the deep catalytic pocket that specifically binds uracil. Nuclear (UNG2) and mitochondrial (UNG1) forms of the enzyme result from the use of two promoters, PA and PB, and alternative splicing. mRNA for UNG1 encodes 304 amino acids, the first 35 of which are unique to this form. mRNA for UNG2 encodes 313 amino acids, the first 44 of which are unique to UNG2. The unique N-terminal sequences in UNG1 and UNG2 are required for mitochondrial and nuclear sorting, respectively, but not for catalytic activity. The 269 amino acid residues common to the two forms include the compact catalytic domain of approximately 220 C-terminal residues and an N-terminal part that binds replication protein A (RPA), indicating a possible role for RPA in base excision repair.
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properties of a recombinant human uracil dna Glycosylase from the ung gene and evidence that ung encodes the major uracil dna Glycosylase
Biochemistry, 1995Co-Authors: Geir Slupphaug, Sangeeta Bharati, Bodil Kavli, Ingrid Eftedal, Nils M Helle, Terje Haug, David W Levine, Hans E. KrokanAbstract:We have expressed a human recombinant Uracil-DNA Glycosylase (UNG delta 84) closely resembling the mature form of the human enzyme (UNG, from the UNG gene) in Escherichia coli and purified the protein to apparent homogeneity. This form, which lacks the first seven nonconserved amino acids at the amino terminus, has properties similar to a 50% homogeneous UDG purified from human placenta except for a lower salt optimum and a slightly lower specific activity. The recombinant enzyme removed U from ssDNA approximately 3-fold more rapidly than from dsDNA. In the presence of 10 mM NaCl, Km values were 0.45 and 1.6 microM with ssDNA and dsDNA, respectively, but Km values increased significantly with higher NaCl concentrations. The pH optimum for UNG delta 84 was 7.7-8.0; the activation energy, 50.6 kJ/mol; and the pI between 10.4 and 10.8. The enzyme displays a striking sequence specificity in removal of U from UA base pairs in M13 dsDNA. The sequence specificity for removal of U from UG mismatches (simulating the situation after deamination of C) was essentially similar to removal from UA matches when examined in oligonucleotides. However, removal of U from UG mismatches was in general slightly faster, and in some cases significantly faster, than removal from UA base pairs. Immunofluorescence studies using polyclonal antibodies against UNG delta 84 demonstrated that the major fraction of UNG was located in the nucleus. Furthermore, > 98% of the total Uracil-DNA Glycosylase activity from HeLa cell extracts was inhibited by the antibodies, indicating that the UNG protein represents the major Uracil-DNA Glycosylase in the cells.
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Expression of O6-methylguanine-DNA methyltransferase and Uracil-DNA Glycosylase in human placentae from smokers and non-smokers
Carcinogenesis, 1992Co-Authors: Geir Slupphaug, Idar Lettrem, Bjørnar Myrnes, Hans E. KrokanAbstract:DNA repair capacity is likely to be a critical factor in mutagenesis and carcinogenesis, as well as for the response to some cytostatics. We have studied inter- and intra-individual variation in the activities of O 6 -methylguanine-DNA methyltransferase (O 6 -MT) and Uracil-DNA Glycosylase (UDG) in 35 placentae from smokers and non-smokers. The maximum interindividual variation in the activities of O 6 -MT and UDG were 8.3- and 7.7-fold, respectively
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Human Uracil-DNA Glycosylase complements E.coli ung mutants
Nucleic Acids Research, 1991Co-Authors: Lisbeth C. Olsen, Hans E. Krokan, Rein Aasland, Dag E. HellandAbstract:: We have previously isolated a cDNA encoding a human Uracil-DNA Glycosylase which is closely related to the bacterial and yeast enzymes. In vitro expression of this cDNA produced a protein with an apparent molecular weight of 34 K in agreement with the size predicted from the sequence data. The in vitro expressed protein exhibited Uracil-DNA Glycosylase activity. The close resemblance between the human and the bacterial enzyme raised the possibility that the human enzyme may be able to complement E. coli ung mutants. In order to test this hypothesis, the human Uracil-DNA Glycosylase cDNA was established in a bacterial expression vector. Expression of the human enzyme as a LacZ alpha-humUNG fusion protein was then studied in E. coli ung mutants. E. coli cells lacking Uracil-DNA Glycosylase activity exhibit a weak mutator phenotype and they are permissive for growth of phages with uracil-containing DNA. Here we show that the expression of human Uracil-DNA Glycosylase in E. coli can restore the wild type phenotype of ung mutants. These results demonstrate that the evolutionary conservation of the Uracil-DNA Glycosylase structure is also reflected in the conservation of the mechanism for removal of uracil from DNA.
Bodil Kavli - One of the best experts on this subject based on the ideXlab platform.
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human uracil dna Glycosylase deficiency associated with profoundly impaired immunoglobulin class switch recombination
Nature Immunology, 2003Co-Authors: Kohsuke Imai, Geir Slupphaug, Nadia Catalan, Monique Forveille, Bodil Kavli, Hans D. Ochs, Hans E. Krokan, Shigeaki Nonoyama, Patrick Revy, Alain FischerAbstract:Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil–DNA Glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.
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Characterisation of the substrate specificity of homogeneous vaccinia virus Uracil-DNA Glycosylase.
Nucleic Acids Research, 2003Co-Authors: Natale Scaramozzino, Bodil Kavli, Jacques Laval, Guenhael Sanz, Jean Marc Crance, Murat Saparbaev, Robert Drillien, Daniel GarinAbstract:The decision to stop smallpox vaccination and the loss of specific immunity in a large proportion of the population could jeopardise world health due to the possibility of a natural or provoked re-emergence of smallpox. Therefore, it is mandatory to improve the current capability to prevent or treat such infections. The DNA repair protein Uracil-DNA Glycosylase (UNG) is one of the viral enzymes important for poxvirus pathogenesis. Consequently, the inhibition of UNG could be a rational strategy for the treatment of infections with poxviruses. In order to develop inhibitor assays for UNG, as a first step, we have characterised the recombinant vaccinia virus UNG (vUNG) and compared it with the human nuclear form (hUNG2) and catalytic fragment (hUNG) UNG. In contrast to hUNG2, vUNG is strongly inhibited in the presence of 7.5 mM MgCl2. We have shown that highly purified vUNG is not inhibited by a specific Uracil-DNA Glycosylase inhibitor. Interestingly, both viral and human enzymes preferentially excise uracil when it is opposite to cytosine. The present study provides the basis for the design of specific inhibitors for vUNG.
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Human Uracil-DNA Glycosylase
Advances in DNA Damage and Repair, 1999Co-Authors: Hans E. Krokan, Sangeeta Bharati, Kristin Solum Steinsbekk, Hilde Nilsen, Camilla Skjelbred, Bodil Kavli, Frank Skorpen, Marit Otterlei, Rune Standal, Geir SlupphaugAbstract:Uracil in DNA results from either misincorporation of dUMP residues during replication, or from deamination of cytosine residues. The latter process results in premutagenic U:G mispairs that, unless uracil is removed, will cause GC→AT transitions in the subsequent round of replication. The 13.8 kb gene for human Uracil-DNA Glycosylase, UNG, is highly conserved and comprises 7 exons. It encodes more than 98% of the total Uracil-DNA Glycosylase activity in the cell. The crystal structure of the catalytic domain of UNG in complex with target DNA has demonstrated that all essential contacts are with the uracil-containing strand. The structure also reveals the mechanism of enzyme-assisted flipping of the uracil-containing nucleotide into the deep catalytic pocket that specifically binds uracil. Nuclear (UNG2) and mitochondrial (UNG1) forms of the enzyme result from the use of two promoters, PA and PB, and alternative splicing. mRNA for UNG1 encodes 304 amino acids, the first 35 of which are unique to this form. mRNA for UNG2 encodes 313 amino acids, the first 44 of which are unique to UNG2. The unique N-terminal sequences in UNG1 and UNG2 are required for mitochondrial and nuclear sorting, respectively, but not for catalytic activity. The 269 amino acid residues common to the two forms include the compact catalytic domain of approximately 220 C-terminal residues and an N-terminal part that binds replication protein A (RPA), indicating a possible role for RPA in base excision repair.
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properties of a recombinant human uracil dna Glycosylase from the ung gene and evidence that ung encodes the major uracil dna Glycosylase
Biochemistry, 1995Co-Authors: Geir Slupphaug, Sangeeta Bharati, Bodil Kavli, Ingrid Eftedal, Nils M Helle, Terje Haug, David W Levine, Hans E. KrokanAbstract:We have expressed a human recombinant Uracil-DNA Glycosylase (UNG delta 84) closely resembling the mature form of the human enzyme (UNG, from the UNG gene) in Escherichia coli and purified the protein to apparent homogeneity. This form, which lacks the first seven nonconserved amino acids at the amino terminus, has properties similar to a 50% homogeneous UDG purified from human placenta except for a lower salt optimum and a slightly lower specific activity. The recombinant enzyme removed U from ssDNA approximately 3-fold more rapidly than from dsDNA. In the presence of 10 mM NaCl, Km values were 0.45 and 1.6 microM with ssDNA and dsDNA, respectively, but Km values increased significantly with higher NaCl concentrations. The pH optimum for UNG delta 84 was 7.7-8.0; the activation energy, 50.6 kJ/mol; and the pI between 10.4 and 10.8. The enzyme displays a striking sequence specificity in removal of U from UA base pairs in M13 dsDNA. The sequence specificity for removal of U from UG mismatches (simulating the situation after deamination of C) was essentially similar to removal from UA matches when examined in oligonucleotides. However, removal of U from UG mismatches was in general slightly faster, and in some cases significantly faster, than removal from UA base pairs. Immunofluorescence studies using polyclonal antibodies against UNG delta 84 demonstrated that the major fraction of UNG was located in the nucleus. Furthermore, > 98% of the total Uracil-DNA Glycosylase activity from HeLa cell extracts was inhibited by the antibodies, indicating that the UNG protein represents the major Uracil-DNA Glycosylase in the cells.
Debasish Chattopadhyay - One of the best experts on this subject based on the ideXlab platform.
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Binding of undamaged double stranded DNA to vaccinia virus Uracil-DNA Glycosylase
BMC Structural Biology, 2015Co-Authors: N. Schormann, Robert P. Ricciardi, Surajit Banerjee, Debasish ChattopadhyayAbstract:Background Uracil-DNA Glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus Uracil-DNA Glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized.
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Structure of the uracil complex of Vaccinia virus uracil DNA Glycosylase
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2013Co-Authors: N. Schormann, Robert P. Ricciardi, Surajit Banerjee, Debasish ChattopadhyayAbstract:Poxvirus uracil DNA Glycosylases are the most diverse members of the family I uracil DNA Glycosylases (UNGs). The crystal structure of the uracil complex of Vaccinia virus uracil DNA Glycosylase (D4) was determined at 2.03 A resolution. One uracil molecule was located in the active-site pocket in each of the 12 noncrystallographic symmetry-related D4 subunits. Although the UNGs of the poxviruses (including D4) feature significant differences in the characteristic motifs designated for uracil recognition and in the base-excision mechanism, the architecture of the active-site pocket in D4 is very similar to that in UNGs of other organisms. Overall, the interactions of the bound uracil with the active-site residues are also similar to the interactions previously observed in the structures of human and Escherichia coli UNG.
