T A Kunkel

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Error-prone replication of repeated DNA sequences by T7 DNA polymerase in the absence of its processivity subunit
    T A Kunkel
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
    Proc Natl Acad Sci U S A 91:6830-4. 1994
  2. pmc Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6
    Shannon F Holmes
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, United States
    DNA Repair (Amst) 6:293-303. 2007
  3. pmc Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes
    Vladimir I Mayorov
    Mercer University School of Medicine, Macon, GA 31207, USA
    BMC Immunol 6:10. 2005
  4. pmc Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations
    Youri I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institute of Health, DHHS, Research Triangle Park, NC 27709, USA
    BMC Biol 2:11. 2004
  5. ncbi request reprint Functions of human DNA polymerases eta, kappa and iota suggested by their properties, including fidelity with undamaged DNA templates
    Thomas A Kunkel
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 2:135-49. 2003
  6. ncbi request reprint DNA replication fidelity
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:16895-8. 2004
  7. ncbi request reprint Considering the cancer consequences of altered DNA polymerase function
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH DHHS, Research Triangle Park, NC 27709, USA
    Cancer Cell 3:105-10. 2003
  8. ncbi request reprint DNA mismatch repair
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Biochem 74:681-710. 2005
  9. ncbi request reprint DNA replication fidelity
    T A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Biochem 69:497-529. 2000
  10. pmc Dividing the workload at a eukaryotic replication fork
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, 111 T W Alexander Drive, National Institute of Environmental Health Sciences, National Institute of Health, DHHS, Research Triangle Park, NC 27709, USA
    Trends Cell Biol 18:521-7. 2008

Detail Information

Publications117 found, 100 shown here

  1. pmc Error-prone replication of repeated DNA sequences by T7 DNA polymerase in the absence of its processivity subunit
    T A Kunkel
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
    Proc Natl Acad Sci U S A 91:6830-4. 1994
    ..Thus, replicative expansion of repetitive sequences occurs in the absence of a replication accessory protein...
  2. pmc Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6
    Shannon F Holmes
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, United States
    DNA Repair (Amst) 6:293-303. 2007
    ....
  3. pmc Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes
    Vladimir I Mayorov
    Mercer University School of Medicine, Macon, GA 31207, USA
    BMC Immunol 6:10. 2005
    ..The DNA sequence context of mutation hotspots at G-C pairs during SHM is DGYW/WRCH (G-C is a hotspot position, R = A/G, Y = T/C, W = A/T, D = A/G/T)...
  4. pmc Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations
    Youri I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institute of Health, DHHS, Research Triangle Park, NC 27709, USA
    BMC Biol 2:11. 2004
    ..Here we investigate the mechanism responsible for the mutator effect...
  5. ncbi request reprint Functions of human DNA polymerases eta, kappa and iota suggested by their properties, including fidelity with undamaged DNA templates
    Thomas A Kunkel
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 2:135-49. 2003
    ....
  6. ncbi request reprint DNA replication fidelity
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:16895-8. 2004
  7. ncbi request reprint Considering the cancer consequences of altered DNA polymerase function
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH DHHS, Research Triangle Park, NC 27709, USA
    Cancer Cell 3:105-10. 2003
    ..This review describes emerging information on the properties and functions of human DNA polymerases, with emphasis on connections between DNA polymerase functions and cancer...
  8. ncbi request reprint DNA mismatch repair
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Biochem 74:681-710. 2005
    ..Emphasis is on structure-function studies of MMR proteins, on how mismatches are recognized, on the process by which the newly replicated strand is identified, and on excision of the replication error...
  9. ncbi request reprint DNA replication fidelity
    T A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Biochem 69:497-529. 2000
    ..We highlight common features that are relevant to the fidelity of any DNA synthesis reaction, and consider why fidelity varies depending on the enzymes, the error, and the local sequence environment...
  10. pmc Dividing the workload at a eukaryotic replication fork
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, 111 T W Alexander Drive, National Institute of Environmental Health Sciences, National Institute of Health, DHHS, Research Triangle Park, NC 27709, USA
    Trends Cell Biol 18:521-7. 2008
    ..We also review earlier studies in light of this model and then consider prospects for future investigations of possible variations on this simple division of labor...
  11. pmc Evolving views of DNA replication (in)fidelity
    T A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Cold Spring Harb Symp Quant Biol 74:91-101. 2009
    ..This offers the potential to modulate rates of point mutations over a wide range, with consequences that can be either deleterious or beneficial...
  12. ncbi request reprint DNA replication and repair reactions relevant to the AHS
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS Research Triangle Park, NC 27709, USA
    J Biochem Mol Toxicol 19:190-1. 2005
  13. pmc Balancing eukaryotic replication asymmetry with replication fidelity
    Thomas A Kunkel
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Curr Opin Chem Biol 15:620-6. 2011
    ....
  14. pmc In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta
    Y I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Genetics 159:47-64. 2001
    ..This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially suppressed by disruption of the REV3 gene...
  15. ncbi request reprint High affinity cooperative DNA binding by the yeast Mlh1-Pms1 heterodimer
    M C Hall
    Laboratories of Molecular Genetics and Structural Biology, NIEHS, RTP, NC 27709, USA
    J Mol Biol 312:637-47. 2001
    ..These DNA binding properties of Mlh1-Pms1 may be relevant to its participation in DNA mismatch repair, recombination and cellular responses to DNA damage...
  16. ncbi request reprint Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes
    A B Clark
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 275:36498-501. 2000
    ..Thus, MSH3 and MSH6 interactions with PCNA may facilitate early steps in DNA mismatch repair and may also be important for other roles of these eukaryotic MutS homologs...
  17. pmc Functional analysis of human MutSalpha and MutSbeta complexes in yeast
    A B Clark
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 27:736-42. 1999
    ..The analogous mutation in humans is associated with microsatellite instability, defective MMR and cancer, illustrating the utility of the yeast system for studying human disease alleles...
  18. ncbi request reprint Mutator phenotype due to loss of heterozygosity in diploid yeast strains with mutations in MSH2 and MLH1
    K Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
    Toxicol Lett 112:239-44. 2000
    ..These results have implications for understanding the mechanisms of carcinogenesis in humans...
  19. pmc The 3'-->5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability
    Y H Jin
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 98:5122-7. 2001
    ....
  20. ncbi request reprint Purification of eukaryotic MutL homologs from Saccharomyces cerevisiae using self-affinity technology
    M C Hall
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Protein Expr Purif 21:333-42. 2001
    ..The general approach is a valid alternative for simple, rapid purification of recombinant proteins in yeast when expression in bacteria is unsuitable...
  21. ncbi request reprint Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines
    J C Boyer
    Laboratory of Molecular Genetics, National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Cancer Res 55:6063-70. 1995
    ..It also provides an extensive panel of repair-proficient and repair-deficient cell lines for future studies of mismatch repair...
  22. pmc Inactivation of DNA mismatch repair by increased expression of yeast MLH1
    P V Shcherbakova
    Laboratories of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Cell Biol 21:940-51. 2001
    ....
  23. ncbi request reprint The fidelity of human DNA polymerase gamma with and without exonucleolytic proofreading and the p55 accessory subunit
    M J Longley
    Laboratory of Molecular Genetics and the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 276:38555-62. 2001
    ..These data suggest that homopolymeric runs in mitochondrial DNA may be particularly prone to frameshift mutation in vivo due to replication errors by pol gamma...
  24. ncbi request reprint Asymmetric recognition of DNA local distortion. Structure-based functional studies of eukaryotic Msh2-Msh6
    K Drotschmann
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 276:46225-9. 2001
    ..The importance of these contacts decreases with increasing distance from the mismatch, implying that interactions at and near the mismatch are important for binding in a kinked DNA conformation...
  25. ncbi request reprint Proofreading of DNA polymerase eta-dependent replication errors
    K Bebenek
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 276:2317-20. 2001
    ....
  26. pmc Strand specificity of mutagenic bypass replication of DNA containing psoralen monoadducts in a human cell extract
    D C Thomas
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Cell Biol 16:2537-44. 1996
    ..A model is proposed based on the preferential loopout of the monoadducted base from the strand that templates retrograde discontinuous synthesis...
  27. ncbi request reprint Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity
    J I Risinger
    Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Cancer Res 55:5664-9. 1995
    ..There was no apparent correlation with microsatellite instability and clinical outcome...
  28. ncbi request reprint Error rate and specificity of human and murine DNA polymerase eta
    T Matsuda
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    J Mol Biol 312:335-46. 2001
    ..The nature and location of these errors suggest that some may be initiated by strand slippage, while others result from additional mechanisms...
  29. ncbi request reprint Characterization of distinct human endometrial carcinoma cell lines deficient in mismatch repair that originated from a single tumor
    W E Glaab
    Laboratory of Environmental Carcinogenesis and Mutagenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 273:26662-9. 1998
    ..These data support a critical role for hPMS2 in human MMR, while further defining the role of the hMSH2/hMSH3 heterodimer in maintaining genomic stability in the absence of a wild-type hMSH2/hMSH6 heterodimer...
  30. ncbi request reprint The accuracy of reverse transcriptase from HIV-1
    J D Roberts
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
    Science 242:1171-3. 1988
    ..The data are consistent with the notion that the exceptional diversity of the HIV-1 genome results from error-prone reverse transcription...
  31. pmc Unequal human immunodeficiency virus type 1 reverse transcriptase error rates with RNA and DNA templates
    J C Boyer
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
    Proc Natl Acad Sci U S A 89:6919-23. 1992
    ..The data also provide estimates of substitution and frameshift error rates during transcription by T7 RNA polymerase...
  32. ncbi request reprint Mutator effects of overproducing DNA polymerase eta (Rad30) and its catalytically inactive variant in yeast
    Y I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Natioanl Institutes of Health, Research Triangle Park, NC 27709, USA
    Mutat Res 478:129-39. 2001
    ..This suggests that more than one mutagenic mechanism is operating when RAD30 is overexpressed...
  33. ncbi request reprint Family growth: the eukaryotic DNA polymerase revolution
    K Bebenek
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Cell Mol Life Sci 59:54-7. 2002
  34. pmc Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene
    K Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 96:2970-5. 1999
    ..The synergistic effects of heterozygosity for mutations in two different genes that act in series to correct replication errors may be relevant to cancer predisposition...
  35. ncbi request reprint Investigating the role of the little finger domain of Y-family DNA polymerases in low fidelity synthesis and translesion replication
    Francois Boudsocq
    Section on DNA Replication, Repair, and Mutagenesis, Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2725, USA
    J Biol Chem 279:32932-40. 2004
    ..Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member...
  36. pmc Eukaryotic DNA polymerase amino acid sequence required for 3'----5' exonuclease activity
    A Morrison
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
    Proc Natl Acad Sci U S A 88:9473-7. 1991
    ..None of these residues, however, appeared to be identifiable in the catalytic subunits of human, yeast, or Drosophila alpha DNA polymerases...
  37. ncbi request reprint Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis
    A Umar
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Cell 87:65-73. 1996
    ..The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions...
  38. ncbi request reprint Mutator phenotypes of common polymorphisms and missense mutations in MSH2
    K Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Curr Biol 9:907-10. 1999
    ..The results suggest that cancer may be associated with even partial loss of hMSH2 function and they are consistent with the hypothesis that polymorphisms in hMSH2 might predispose humans to disease...
  39. pmc Substrate-induced DNA strand misalignment during catalytic cycling by DNA polymerase lambda
    Katarzyna Bebenek
    Laboratory of Structural Biology and Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA
    EMBO Rep 9:459-64. 2008
    ..The results indicate that dNTP-induced template strand repositioning during conformational rearrangements in the catalytic cycle is crucial to controlling the rate of strand slippage...
  40. ncbi request reprint Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins
    Mark C Hall
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:3673-9. 2002
    ..This is consistent with a model wherein ATP may first bind to Mlh1, resulting in events that permit ATP binding to Pms1 and later steps in DNA mismatch repair...
  41. ncbi request reprint A thumb subdomain mutant of the large fragment of Escherichia coli DNA polymerase I with reduced DNA binding affinity, processivity, and frameshift fidelity
    D T Minnick
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 271:24954-61. 1996
    ..The results are discussed in light of remarkably similar observations with T7 DNA polymerase in the presence or absence of thioredoxin, an accessory subunit that affects these same properties...
  42. ncbi request reprint Oligonucleotide-directed mutagenesis without phenotypic selection
    T A Kunkel
    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
    Curr Protoc Neurosci . 2001
    ..The length of the oligonucleotide primer is highly variable and depends on the nature of the change being made...
  43. pmc Effects of accessory proteins on the bypass of a cis-syn thymine-thymine dimer by Saccharomyces cerevisiae DNA polymerase eta
    Scott D McCulloch
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Biochemistry 46:8888-96. 2007
    ..Thus, although accessory proteins clearly participate in pol eta functions in vivo, they do not appear to help suppress UV mutagenesis by improving pol eta bypass fidelity per se...
  44. ncbi request reprint Unique error signature of the four-subunit yeast DNA polymerase epsilon
    Polina V Shcherbakova
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, North Carolina 27709, USA
    J Biol Chem 278:43770-80. 2003
    ..We discuss the implications of these findings for the role of Pol epsilon polymerase activity in DNA replication...
  45. pmc A unique error signature for human DNA polymerase nu
    Mercedes E Arana
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 6:213-23. 2007
    ..Amino acid sequence alignments based on the structures of more accurate A family polymerases suggest substantial differences in the O-helix of pol nu that could contribute to this unique error signature...
  46. pmc Role of the catalytic metal during polymerization by DNA polymerase lambda
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 6:1333-40. 2007
    ..These data provide pre- and post-transition state information and outline in a single crystal the pathway for the phosphoryl transfer reaction carried out by DNA polymerases...
  47. pmc Altered spectra of hypermutation in antibodies from mice deficient for the DNA mismatch repair protein PMS2
    D B Winter
    Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 95:6953-8. 1998
    ..The data indicate that tandem substitutions are produced by the hypermutation mechanism and then processed by a PMS2-dependent pathway...
  48. ncbi request reprint Purification and characterization of DNA polymerase II from the yeast Saccharomyces cerevisiae. Identification of the catalytic core and a possible holoenzyme form of the enzyme
    R K Hamatake
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
    J Biol Chem 265:4072-83. 1990
    ....
  49. ncbi request reprint 5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro
    K Bebenek
    Laboratory of Molecular Genetics and, Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Science 291:2156-9. 2001
    ..These data and three distinct catalytic properties of pol iota implicate it in specialized forms of base excision repair (BER)...
  50. pmc Inefficient proofreading and biased error rates during inaccurate DNA synthesis by a mutant derivative of Saccharomyces cerevisiae DNA polymerase delta
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 282:2324-32. 2007
    ..cerevisiae strain has an elevated spontaneous mutation rate that is likely due to reduced replication fidelity in vivo...
  51. ncbi request reprint A structural solution for the DNA polymerase lambda-dependent repair of DNA gaps with minimal homology
    Miguel Garcia-Diaz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Cell 13:561-72. 2004
    ..Surprisingly, Pol lambda can adopt a closed conformation, even in the absence of dNTP binding. These observations have implications for the catalytic mechanism and putative DNA repair functions of Pol lambda...
  52. pmc Enzymatic switching for efficient and accurate translesion DNA replication
    Scott D McCulloch
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 32:4665-75. 2004
    ....
  53. pmc Template strand scrunching during DNA gap repair synthesis by human polymerase lambda
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, North Carolina, USA
    Nat Struct Mol Biol 16:967-72. 2009
    ..Thus, akin to scrunching by RNA polymerase during transcription initiation, scrunching occurs during gap filling DNA synthesis associated with DNA repair...
  54. pmc DNA polymerase epsilon: a polymerase of unusual size (and complexity)
    Zachary F Pursell
    Department of Health and Human Services, Laboratory of Molecular Genetics, National Institute of Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Prog Nucleic Acid Res Mol Biol 82:101-45. 2008
  55. pmc Functional residues on the surface of the N-terminal domain of yeast Pms1
    Mercedes E Arana
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, United States
    DNA Repair (Amst) 9:448-57. 2010
    ..Elevated mutation rates also resulted from surface residue replacements that did not affect DNA binding, suggesting that these conserved residues serve other functions, possibly involving interactions with other MMR proteins...
  56. ncbi request reprint Cadmium inhibits the functions of eukaryotic MutS complexes
    Alan B Clark
    Laboratory of Molecular Genetics, NIEHS, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:53903-6. 2004
    ..These data indicate that eukaryotic Msh2-Msh3 and Msh2-Msh6 complexes are targets for inhibition of MMR by cadmium, a human lung carcinogen that is ubiquitous in the environment...
  57. pmc Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH
    K A Eckert
    National Institute of Environmental Health Sciences, Laboratory of Molecular Genetics, Research Triangle Park, NC 27709
    Nucleic Acids Res 21:5212-20. 1993
    ..The HIV-1 RT results are in agreement with our previous hypothesis that the observed increase in polymerase fidelity at low pH results from a decreased efficiency of continuing DNA synthesis from premutational DNA intermediates...
  58. pmc Interaction between DNA Polymerase lambda and anticancer nucleoside analogs
    Miguel Garcia-Diaz
    Laboratory of Structural Biology and Laboratory of Molecular Genetics, Department of Health and Human Services, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 285:16874-9. 2010
    ..Consistent with these structures, Pol lambda efficiently incorporates AraCTP but not dFdCTP. The data are consistent with the possibility that Pol lambda could modulate the cytotoxic effect of AraC...
  59. ncbi request reprint A closed conformation for the Pol lambda catalytic cycle
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    Nat Struct Mol Biol 12:97-8. 2005
    ....
  60. ncbi request reprint Biochemical properties of Saccharomyces cerevisiae DNA polymerase IV
    Katarzyna Bebenek
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:20051-8. 2005
    ..These properties are consistent with a possible role for pol IV in base excision repair and with its known role in non-homologous end joining of double strand breaks, perhaps including those with damaged ends...
  61. pmc RNA-templated DNA repair
    Francesca Storici
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences NIH, DHHS, Research Triangle Park, North Carolina 27709, USA
    Nature 447:338-41. 2007
    ....
  62. ncbi request reprint Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Acta Biochim Pol 50:155-67. 2003
    ..The error prone DNA synthesis observed for the Y955C polgamma is consistent with the accumulation of mtDNA mutations in patients with PEO. The effects of other polgamma mutations associated with PEO are discussed...
  63. ncbi request reprint Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Cell 124:331-42. 2006
    ..They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes...
  64. pmc Evidence for extrinsic exonucleolytic proofreading
    Stephanie A Nick McElhinny
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA
    Cell Cycle 5:958-62. 2006
    ....
  65. pmc Characterization of a replicative DNA polymerase mutant with reduced fidelity and increased translesion synthesis capacity
    Xuejun Zhong
    Laboratory of Molecular Genetics and Laboratory of Structural Biology National Institute of Environmental Health Sciences, NIH, DHHS Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 36:3892-904. 2008
    ..In addition, slight structural differences were observed that could be relevant to the reduced fidelity of L415F RB69 pol...
  66. ncbi request reprint Structural insight into the substrate specificity of DNA Polymerase mu
    Andrea F Moon
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences National Institutes of Health, US Department of Health and Human Services, 111 T W Alexander Drive, MD F3 09, Research Triangle Park, North Carolina 27709, USA
    Nat Struct Mol Biol 14:45-53. 2007
    ..These results provide insight into the substrate specificity and differing functions of four closely related mammalian family X DNA polymerases...
  67. pmc Catalytic mechanism of human DNA polymerase lambda with Mg2+ and Mn2+ from ab initio quantum mechanical/molecular mechanical studies
    G Andres Cisneros
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park RTP, NC 27709, USA
    DNA Repair (Amst) 7:1824-34. 2008
    ..There is partial conservation of these residues across the Pol X family of DNA polymerases...
  68. pmc The X family portrait: structural insights into biological functions of X family polymerases
    Andrea F Moon
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health 111 T W Alexander Drive, Research Triangle Park, NC 27709, United States
    DNA Repair (Amst) 6:1709-25. 2007
    ..Here we consider how distinctive structural features of these enzymes contribute to their biological functions in vivo...
  69. ncbi request reprint Enzymatic cytosine deamination: friend and foe
    Thomas A Kunkel
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Cell 10:962-3. 2002
  70. ncbi request reprint Evidence for sequential action of two ATPase active sites in yeast Msh2-Msh6
    Karin Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 1:743-53. 2002
    ..This suggests sequential action of the two ATPase active sites, in which ATP binds to Msh6 first to trigger downstream events in mismatch repair...
  71. ncbi request reprint The efficiency and specificity of apurinic/apyrimidinic site bypass by human DNA polymerase eta and Sulfolobus solfataricus Dpo4
    Robert J Kokoska
    Laboratories of Molecular Genetics and Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:50537-45. 2003
    ....
  72. pmc Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene
    Youri I Pavlov
    Laboratories of Molecular Genetics and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 99:9954-9. 2002
    ....
  73. ncbi request reprint Functions of eukaryotic DNA polymerases
    Polina V Shcherbakova
    Laboratory of Molecular Genetics at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Sci Aging Knowledge Environ 2003:RE3. 2003
    ..In this review, we discuss the possible functions of these polymerases in DNA damage repair, the replication of intact and damaged chromosomes, and cell cycle checkpoints...
  74. pmc Cadmium is a mutagen that acts by inhibiting mismatch repair
    Yong Hwan Jin
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Nat Genet 34:326-9. 2003
    ..In extracts of human cells, cadmium inhibited at least one step leading to mismatch removal. Together, our data show that a high level of genetic instability can result from environmental impediment of a mutation-avoidance system...
  75. ncbi request reprint Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity
    Scott D McCulloch
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA
    Nature 428:97-100. 2004
    ..Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta during dimer bypass could contribute to mutagenesis and skin cancer...
  76. ncbi request reprint The base substitution fidelity of DNA polymerase beta-dependent single nucleotide base excision repair
    Toshiro Matsuda
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:25947-51. 2003
    ..Thus other proteins in the BER reaction may enhance the base substitution fidelity of DNA polymerase beta during single nucleotide BER...
  77. pmc DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair
    Mark C Hall
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 31:2025-34. 2003
    ..Finally, the results are consistent with the hypothesis that DNA binding by Mlh1 is important for MMR...
  78. ncbi request reprint Recombinogenic phenotype of human activation-induced cytosine deaminase
    Vladimir P Poltoratsky
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    J Immunol 172:4308-13. 2004
    ..Thus, the initial step of base excision repair is required for AID-dependent recombination and is a branch point for either hypermutagenesis or recombination...
  79. pmc Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro
    J D Roberts
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
    Mol Cell Biol 9:469-76. 1989
    ..The overall error rate of RT in vitro is sufficient to account for the estimated mutation rate of these viruses...
  80. ncbi request reprint The frameshift infidelity of human DNA polymerase lambda. Implications for function
    Katarzyna Bebenek
    Laboratory of Molecular Genetics and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:34685-90. 2003
    ..This may include non-homologous end-joining of strand breaks resulting from DNA damage, because Pol lambda has intrinsic 5',2'-deoxyribose-5-phosphate lyase activity...
  81. ncbi request reprint Yeast origins establish a strand bias for replicational mutagenesis
    Youri I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Cell 10:207-13. 2002
    ....
  82. pmc Division of labor at the eukaryotic replication fork
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Mol Cell 30:137-44. 2008
    ....
  83. ncbi request reprint Saccharomyces cerevisiae DNA polymerase delta: high fidelity for base substitutions but lower fidelity for single- and multi-base deletions
    John M Fortune
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:29980-7. 2005
    ..Thus, strand slippage during replication by wild type Pol delta may be a primary source of insertion and deletion mutagenesis in eukaryotic genomes...
  84. pmc Multiple solutions to inefficient lesion bypass by T7 DNA polymerase
    Scott D McCulloch
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States
    DNA Repair (Amst) 5:1373-83. 2006
    ....
  85. ncbi request reprint Efficiency, fidelity and enzymatic switching during translesion DNA synthesis
    Scott D McCulloch
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA
    Cell Cycle 3:580-3. 2004
    ..Several observations from that study were unanticipated. Here we discuss the structural and biological implications of those results in light of earlier studies of translesion synthesis...
  86. pmc Genome-wide model for the normal eukaryotic DNA replication fork
    ANDRES A LARREA
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 107:17674-9. 2010
    ..This strand bias strongly supports the idea that Pol ╬┤ is primarily a lagging strand polymerase during replication across the entire nuclear genome...
  87. pmc Genome instability due to ribonucleotide incorporation into DNA
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
    Nat Chem Biol 6:774-81. 2010
    ....
  88. pmc Yeast DNA polymerase epsilon participates in leading-strand DNA replication
    Zachary F Pursell
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Science 317:127-30. 2007
    ....
  89. pmc Loop 1 modulates the fidelity of DNA polymerase lambda
    Katarzyna Bebenek
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA
    Nucleic Acids Res 38:5419-31. 2010
    ....
  90. ncbi request reprint Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis
    Mikhail V Ponamarev
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:15225-8. 2002
    ..The error-prone DNA synthesis observed for the Y955C pol gamma is consistent with the accumulation of mtDNA mutations in patients with PEO...
  91. ncbi request reprint Mechanism of a genetic glissando: structural biology of indel mutations
    Miguel Garcia-Diaz
    Laboratory of Structural Biology and Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Trends Biochem Sci 31:206-14. 2006
    ..These structures provide insight into the molecular mechanisms underlying indel generation...
  92. ncbi request reprint DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1 heterodimers
    Karin Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Biol Chem 383:969-75. 2002
    ..The novel DNA binding properties of Mlh1-Pms1 may be relevant to signal transduction during DNA mismatch repair and to recombination, meiosis and cellular responses to DNA damage...
  93. pmc The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta
    Scott D McCulloch
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences Research, NC 27709, USA
    Nucleic Acids Res 37:2830-40. 2009
    ..The fact that yeast and mammalian Pol eta have intrinsically different catalytic properties has potential biological implications...
  94. ncbi request reprint Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast
    Youri I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Curr Biol 13:744-8. 2003
    ..This is consistent with the hypothesis that 5' ends of Okazaki fragments and PCNA, present at high density during lagging strand replication, are used as strand discrimination signals for mismatch repair in vivo...
  95. ncbi request reprint Oligonucleotide-directed mutagenesis without phenotypic selection
    T A Kunkel
    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
    Curr Protoc Mol Biol . 2001
    ..Use of the uracil-containing template allows rapid and efficient recovery of mutants; in principle this same template can be applied to most of the other mutagenesis protocols in use...
  96. pmc The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteins
    Xuejun Zhong
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 34:4731-42. 2006
    ....
  97. pmc Low-fidelity DNA synthesis by human DNA polymerase theta
    Mercedes E Arana
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 36:3847-56. 2008
    ..Thus, pol is an exception among family A polymerases, and its low fidelity is consistent with its proposed roles in TLS and SHM...
  98. ncbi request reprint Localization of the deoxyribose phosphate lyase active site in human DNA polymerase iota by controlled proteolysis
    Rajendra Prasad
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:29649-54. 2003
    ....
  99. ncbi request reprint Solution structure of the lyase domain of human DNA polymerase lambda
    Eugene F Derose
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Box 12233, Research Triangle Park, North Carolina 27709, USA
    Biochemistry 42:9564-74. 2003
    ..g., K60 in pol beta and K307 in pol lambda. Additionally, on the basis of the structural alignment obtained, several previously proposed mechanistic hypotheses can be evaluated...
  100. ncbi request reprint Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair
    J I Risinger
    Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Nat Genet 14:102-5. 1996
    ....
  101. pmc Promiscuous mismatch extension by human DNA polymerase lambda
    Angel J Picher
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma, 28049 Madrid, Spain
    Nucleic Acids Res 34:3259-66. 2006
    ..This property of Pol lambda suggests a potential role as a 'mismatch extender' during non-homologous end joining (NHEJ), and possibly during translesion synthesis...