8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279. Miller, H., Prasad, R., Wilson, S. H., Johnson, F., & Grollman, A. P. Biochemistry, 39(5):1029-33, 2, 2000. Mendeley Paper abstract bibtex To understand how the active site of a DNA polymerase might modulate the coding of 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type DNA polymerase beta (pol beta) and two active-site mutants. We compared the coding of these polymerases by calculating the ratio of efficiencies for incorporation of dATP and dCTP opposite 8-oxodG and for incorporation of 8-oxodGTP opposite dA and dC. For wild-type pol beta, there is a 2:1 preference for incorporation of dCTP over dATP opposite 8-oxodG using a 5'-phosphorylated 4-base gap substrate. Mutation of either Asn279 or Arg283 to alanine has almost no effect on the ratio. 8-OxodGTP is preferentially incorporated opposite a template dA (24:1) by wild-type pol beta; mutation of Asn279 to alanine results dramatic change whereby there is preferential incorporation of 8-oxodGTP opposite dC (14:1). This suggests that interactions of 8-oxodGTP with Asn279 in the polymerase active site may alter the conformation of 8-oxodGTP and therefore alter its misincorporation.
@article{ mendeley_4996784552,
isauthor = {1},
abstract = {To understand how the active site of a DNA polymerase might modulate the coding of 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type DNA polymerase beta (pol beta) and two active-site mutants. We compared the coding of these polymerases by calculating the ratio of efficiencies for incorporation of dATP and dCTP opposite 8-oxodG and for incorporation of 8-oxodGTP opposite dA and dC. For wild-type pol beta, there is a 2:1 preference for incorporation of dCTP over dATP opposite 8-oxodG using a 5'-phosphorylated 4-base gap substrate. Mutation of either Asn279 or Arg283 to alanine has almost no effect on the ratio. 8-OxodGTP is preferentially incorporated opposite a template dA (24:1) by wild-type pol beta; mutation of Asn279 to alanine results dramatic change whereby there is preferential incorporation of 8-oxodGTP opposite dC (14:1). This suggests that interactions of 8-oxodGTP with Asn279 in the polymerase active site may alter the conformation of 8-oxodGTP and therefore alter its misincorporation.},
month = {2},
canonical_id = {4ffc6b00-6d09-11df-a474-0026b95e3e23},
added = {1339234597},
year = {2000},
keywords = {Asparagine, Asparagine: genetics, Asparagine: metabolism, Binding Sites, Binding Sites: genetics, Deoxyguanine Nucleotides, Deoxyguanine Nucleotides: genetics, Deoxyguanine Nucleotides: metabolism, Deoxyguanosine, Deoxyguanosine: analogs & derivatives, Deoxyguanosine: metabolism, DNA Polymerase beta, DNA Polymerase beta: genetics, DNA Polymerase beta: metabolism, Humans, Kinetics, Mutagens, Mutagens: metabolism, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Oligodeoxyribonucleotides: chemical synthesis, Oligodeoxyribonucleotides: metabolism, Substrate Specificity, Substrate Specificity: genetics, Templates, Genetic},
isstarred = {0},
id = {4996784552},
discipline = {Computer and Information Science},
journal = {Biochemistry},
title = {8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.},
day = {8},
deletionpending = {0},
version = {1339234654},
pmid = {10653647},
number = {5},
url_mendeley = {http://www.mendeley.com//research/8-oxodgtp-incorporation-dna-polymerase-beta-modified-active-site-residue-asn279-1//},
volume = {39},
isread = {0},
author = {H {Miller} and R {Prasad} and S H {Wilson} and F {Johnson} and A P {Grollman}},
pages = {1029-33},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10653647},
type = {Journal Article},
issn = {0006-2960},
modified = {1339234654},
subdiscipline = {Information Science},
journal = {Biochemistry},
dateaccessed = {09/06/12}
}
Downloads: 0
{"_id":{"_str":"51f6ba9259ced8df44000fe9"},"__v":9,"authorIDs":[],"author_short":["Miller, H.","Prasad, R.","Wilson, S.<nbsp>H.","Johnson, F.","Grollman, A.<nbsp>P."],"bibbaseid":"miller-prasad-wilson-johnson-grollman-8oxodgtpincorporationbydnapolymerasebetaismodifiedbyactivesiteresidueasn279-2000","bibdata":{"downloads":0,"keyword":["Asparagine","Asparagine: genetics","Asparagine: metabolism","Binding Sites","Binding Sites: genetics","Deoxyguanine Nucleotides","Deoxyguanine Nucleotides: genetics","Deoxyguanine Nucleotides: metabolism","Deoxyguanosine","Deoxyguanosine: analogs & derivatives","Deoxyguanosine: metabolism","DNA Polymerase beta","DNA Polymerase beta: genetics","DNA Polymerase beta: metabolism","Humans","Kinetics","Mutagens","Mutagens: metabolism","Nucleic Acid Conformation","Oligodeoxyribonucleotides","Oligodeoxyribonucleotides: chemical synthesis","Oligodeoxyribonucleotides: metabolism","Substrate Specificity","Substrate Specificity: genetics","Templates","Genetic"],"bibbaseid":"miller-prasad-wilson-johnson-grollman-8oxodgtpincorporationbydnapolymerasebetaismodifiedbyactivesiteresidueasn279-2000","urls":{" mendeley":"http://www.mendeley.com//research/8-oxodgtp-incorporation-dna-polymerase-beta-modified-active-site-residue-asn279-1//","Paper":"http://www.ncbi.nlm.nih.gov/pubmed/10653647"},"role":"author","year":"2000","volume":"39","version":"1339234654","url_mendeley":"http://www.mendeley.com//research/8-oxodgtp-incorporation-dna-polymerase-beta-modified-active-site-residue-asn279-1//","url":"http://www.ncbi.nlm.nih.gov/pubmed/10653647","type":"Journal Article","title":"8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.","subdiscipline":"Information Science","pmid":"10653647","pages":"1029-33","number":"5","month":"2","modified":"1339234654","keywords":"Asparagine, Asparagine: genetics, Asparagine: metabolism, Binding Sites, Binding Sites: genetics, Deoxyguanine Nucleotides, Deoxyguanine Nucleotides: genetics, Deoxyguanine Nucleotides: metabolism, Deoxyguanosine, Deoxyguanosine: analogs & derivatives, Deoxyguanosine: metabolism, DNA Polymerase beta, DNA Polymerase beta: genetics, DNA Polymerase beta: metabolism, Humans, Kinetics, Mutagens, Mutagens: metabolism, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Oligodeoxyribonucleotides: chemical synthesis, Oligodeoxyribonucleotides: metabolism, Substrate Specificity, Substrate Specificity: genetics, Templates, Genetic","key":"mendeley_4996784552","journal":"Biochemistry","isstarred":"0","issn":"0006-2960","isread":"0","isauthor":"1","id":"mendeley_4996784552","discipline":"Computer and Information Science","deletionpending":"0","day":"8","dateaccessed":"09/06/12","canonical_id":"4ffc6b00-6d09-11df-a474-0026b95e3e23","bibtype":"article","bibtex":"@article{ mendeley_4996784552,\n isauthor = {1},\n abstract = {To understand how the active site of a DNA polymerase might modulate the coding of 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type DNA polymerase beta (pol beta) and two active-site mutants. We compared the coding of these polymerases by calculating the ratio of efficiencies for incorporation of dATP and dCTP opposite 8-oxodG and for incorporation of 8-oxodGTP opposite dA and dC. For wild-type pol beta, there is a 2:1 preference for incorporation of dCTP over dATP opposite 8-oxodG using a 5'-phosphorylated 4-base gap substrate. Mutation of either Asn279 or Arg283 to alanine has almost no effect on the ratio. 8-OxodGTP is preferentially incorporated opposite a template dA (24:1) by wild-type pol beta; mutation of Asn279 to alanine results dramatic change whereby there is preferential incorporation of 8-oxodGTP opposite dC (14:1). This suggests that interactions of 8-oxodGTP with Asn279 in the polymerase active site may alter the conformation of 8-oxodGTP and therefore alter its misincorporation.},\n month = {2},\n canonical_id = {4ffc6b00-6d09-11df-a474-0026b95e3e23},\n added = {1339234597},\n year = {2000},\n keywords = {Asparagine, Asparagine: genetics, Asparagine: metabolism, Binding Sites, Binding Sites: genetics, Deoxyguanine Nucleotides, Deoxyguanine Nucleotides: genetics, Deoxyguanine Nucleotides: metabolism, Deoxyguanosine, Deoxyguanosine: analogs & derivatives, Deoxyguanosine: metabolism, DNA Polymerase beta, DNA Polymerase beta: genetics, DNA Polymerase beta: metabolism, Humans, Kinetics, Mutagens, Mutagens: metabolism, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Oligodeoxyribonucleotides: chemical synthesis, Oligodeoxyribonucleotides: metabolism, Substrate Specificity, Substrate Specificity: genetics, Templates, Genetic},\n isstarred = {0},\n id = {4996784552},\n discipline = {Computer and Information Science},\n journal = {Biochemistry},\n title = {8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.},\n day = {8},\n deletionpending = {0},\n version = {1339234654},\n pmid = {10653647},\n number = {5},\n url_mendeley = {http://www.mendeley.com//research/8-oxodgtp-incorporation-dna-polymerase-beta-modified-active-site-residue-asn279-1//},\n volume = {39},\n isread = {0},\n author = {H {Miller} and R {Prasad} and S H {Wilson} and F {Johnson} and A P {Grollman}},\n pages = {1029-33},\n url = {http://www.ncbi.nlm.nih.gov/pubmed/10653647},\n type = {Journal Article},\n issn = {0006-2960},\n modified = {1339234654},\n subdiscipline = {Information Science},\n journal = {Biochemistry},\n dateaccessed = {09/06/12}\n}","author_short":["Miller, H.","Prasad, R.","Wilson, S.<nbsp>H.","Johnson, F.","Grollman, A.<nbsp>P."],"author":["Miller, H","Prasad, R","Wilson, S H","Johnson, F","Grollman, A P"],"added":"1339234597","abstract":"To understand how the active site of a DNA polymerase might modulate the coding of 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type DNA polymerase beta (pol beta) and two active-site mutants. We compared the coding of these polymerases by calculating the ratio of efficiencies for incorporation of dATP and dCTP opposite 8-oxodG and for incorporation of 8-oxodGTP opposite dA and dC. For wild-type pol beta, there is a 2:1 preference for incorporation of dCTP over dATP opposite 8-oxodG using a 5'-phosphorylated 4-base gap substrate. Mutation of either Asn279 or Arg283 to alanine has almost no effect on the ratio. 8-OxodGTP is preferentially incorporated opposite a template dA (24:1) by wild-type pol beta; mutation of Asn279 to alanine results dramatic change whereby there is preferential incorporation of 8-oxodGTP opposite dC (14:1). This suggests that interactions of 8-oxodGTP with Asn279 in the polymerase active site may alter the conformation of 8-oxodGTP and therefore alter its misincorporation."},"bibtype":"article","biburl":"http://www.bibbase.org/mendeley/8d0e083d80","downloads":0,"keywords":["asparagine","asparagine: genetics","asparagine: metabolism","binding sites","binding sites: genetics","deoxyguanine nucleotides","deoxyguanine nucleotides: genetics","deoxyguanine nucleotides: metabolism","deoxyguanosine","deoxyguanosine: analogs & derivatives","deoxyguanosine: metabolism","dna polymerase beta","dna polymerase beta: genetics","dna polymerase beta: metabolism","humans","kinetics","mutagens","mutagens: metabolism","nucleic acid conformation","oligodeoxyribonucleotides","oligodeoxyribonucleotides: chemical synthesis","oligodeoxyribonucleotides: metabolism","substrate specificity","substrate specificity: genetics","templates","genetic"],"search_terms":["oxodgtp","incorporation","dna","polymerase","beta","modified","active","site","residue","asn279","miller","prasad","wilson","johnson","grollman"],"title":"8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.","title_words":["oxodgtp","incorporation","dna","polymerase","beta","modified","active","site","residue","asn279"],"year":2000,"dataSources":["gAmA3Xd2SLMER8RY7"]}