PAUL LAWRENCE MODRICH

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. pmc Mechanisms in eukaryotic mismatch repair
    Paul Modrich
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:30305-9. 2006
  2. ncbi request reprint Differential and simultaneous adenosine di- and triphosphate binding by MutS
    Keith P Bjornson
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:18557-62. 2003
  3. ncbi request reprint A defined human system that supports bidirectional mismatch-provoked excision
    Leonid Dzantiev
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 15:31-41. 2004
  4. pmc Involvement of the beta clamp in methyl-directed mismatch repair in vitro
    Anna Pluciennik
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:32782-91. 2009
  5. ncbi request reprint Mechanism of 5'-directed excision in human mismatch repair
    Jochen Genschel
    Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 12:1077-86. 2003
  6. pmc Human mismatch repair: reconstitution of a nick-directed bidirectional reaction
    Nicoleta Constantin
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:39752-61. 2005
  7. ncbi request reprint Analysis of the excision step in human DNA mismatch repair
    Jochen Genschel
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA
    Methods Enzymol 408:273-84. 2006
  8. ncbi request reprint Human exonuclease I is required for 5' and 3' mismatch repair
    Jochen Genschel
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:13302-11. 2002
  9. ncbi request reprint Differential specificities and simultaneous occupancy of human MutSalpha nucleotide binding sites
    Diana Martik
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 279:28402-10. 2004
  10. ncbi request reprint Endonucleolytic function of MutLalpha in human mismatch repair
    Farid A Kadyrov
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 126:297-308. 2006

Research Grants

  1. ENZYMOLOGY OF EUKARYOTIC DNA MISMATCH REPAIR
    Paul Modrich; Fiscal Year: 1993
  2. Enzymology and Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2003
  3. Enzymology Of Eukaryotic Mismatch Repair
    PAUL LAWRENCE MODRICH; Fiscal Year: 2010
  4. MOLECULAR MECHANISM OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 2003
  5. ENZYMOLOGY OF EUKARYOTIC DNA MISMATCH REPAIR
    Paul Modrich; Fiscal Year: 2002
  6. MOLECULAR MECHANISMS OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 2007
  7. Enzymology Of Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2007
  8. Enzymology and Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2006
  9. MOLECULAR MECHANISMS OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 1999
  10. ENZYMATIC BASIS OF TYPE II RESTRICTION AND MODIFICATION
    Paul Modrich; Fiscal Year: 1980

Collaborators

  • T A Kunkel
  • Cs Szab√≥
  • W Edelmann
  • Henry Friedman
  • Jochen Genschel
  • Farid A Kadyrov
  • Nicoleta Constantin
  • Leonid Dzantiev
  • Anna Pluciennik
  • Ravi R Iyer
  • Celia Baitinger
  • Keith P Bjornson
  • Mike O'Donnell
  • Sally J York
  • Vickers Burdett
  • C Lynn Cheng
  • Diana Martik
  • Miaw Sheue Tsai
  • Lorena S Beese
  • Yanan Fang
  • Elisabeth Penland
  • Olga Lukianova
  • Mercedes E Arana
  • Shannon F Holmes
  • Olga A Lukianova
  • M Eileen Dolan
  • Hongshan Li
  • Francis Ali-Osman
  • Jennifer A Quinn
  • Stewart P Johnson
  • Andrew L Salzman
  • Stephen T Keir
  • Darell D Bigner
  • Peter M Burgers
  • Harvey Sage
  • Leonard J Blackwell
  • Dwayne Allen
  • Laura R Bazemore

Detail Information

Publications18

  1. pmc Mechanisms in eukaryotic mismatch repair
    Paul Modrich
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:30305-9. 2006
  2. ncbi request reprint Differential and simultaneous adenosine di- and triphosphate binding by MutS
    Keith P Bjornson
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:18557-62. 2003
    ..These findings suggest that the protein exists primarily as the ATP.MutS.ADP ternary complex in solution and that this may be the form of the protein that is involved in DNA encounters in vivo...
  3. ncbi request reprint A defined human system that supports bidirectional mismatch-provoked excision
    Leonid Dzantiev
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 15:31-41. 2004
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break...
  4. pmc Involvement of the beta clamp in methyl-directed mismatch repair in vitro
    Anna Pluciennik
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:32782-91. 2009
    ....
  5. ncbi request reprint Mechanism of 5'-directed excision in human mismatch repair
    Jochen Genschel
    Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 12:1077-86. 2003
    ..As observed in the purified system, excision directed by a 5' strand break in HeLa nuclear extract can proceed in the absence of MutLalpha or PCNA, although 3' excision in the extract system requires both proteins...
  6. pmc Human mismatch repair: reconstitution of a nick-directed bidirectional reaction
    Nicoleta Constantin
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:39752-61. 2005
    ..Although this modest inhibition could be because of nonspecific effects, it may indicate limited dependence of bidirectional excision on an aphidicolin-sensitive DNA polymerase...
  7. ncbi request reprint Analysis of the excision step in human DNA mismatch repair
    Jochen Genschel
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA
    Methods Enzymol 408:273-84. 2006
    ..This chapter describes methods for analysis of the reconstituted excision reaction...
  8. ncbi request reprint Human exonuclease I is required for 5' and 3' mismatch repair
    Jochen Genschel
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:13302-11. 2002
    ..The involvement of hEXOI in 3'-heteroduplex repair suggests that it has a regulatory/structural role in assembly of the 3'-excision complex or that the protein possesses a cryptic 3' to 5' hydrolytic activity...
  9. ncbi request reprint Differential specificities and simultaneous occupancy of human MutSalpha nucleotide binding sites
    Diana Martik
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 279:28402-10. 2004
    ..These findings imply that MutSalpha has two nucleotide binding sites with differential specificities for ADP and ATP and suggest that the ADP.MutSalpha.ATP ternary complex has an important role in mismatch repair...
  10. ncbi request reprint Endonucleolytic function of MutLalpha in human mismatch repair
    Farid A Kadyrov
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 126:297-308. 2006
    ..Therefore, the mode of excision initiation may differ in these organisms...
  11. pmc Saccharomyces cerevisiae MutLalpha is a mismatch repair endonuclease
    Farid A Kadyrov
    Department of Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:37181-90. 2007
    ..yMutSalpha.heteroduplex ternary complex. The loaded form of yPCNA may play an important effector role in directing yMutLalpha incision to the discontinuous strand of a nicked heteroduplex...
  12. pmc Functions of MutLalpha, replication protein A (RPA), and HMGB1 in 5'-directed mismatch repair
    Jochen Genschel
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:21536-44. 2009
    ..Assay of extracts derived from HMGB1(+/+) and HMGB1(-/-) mouse embryo fibroblast cells indicates that HMGB1 is not essential for mismatch repair...
  13. pmc Mismatch repair-dependent iterative excision at irreparable O6-methylguanine lesions in human nuclear extracts
    Sally J York
    Howard Hughes Medical Institute and Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:22674-83. 2006
    ..These results provide the first direct evidence for mismatch repair-mediated iterative processing of DNA methylator damage, an effect that may be relevant to damage signaling events triggered by this class of chemotherapeutic agent...
  14. ncbi request reprint Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft
    C Lynn Cheng
    Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cancer Ther 4:1364-8. 2005
    ..9 and 45.7 days, respectively. These results suggest that inhibition of PARP may increase the efficacy of temozolomide in the treatment of malignant gliomas, particularly in tumors deficient in DNA mismatch repair...
  15. ncbi request reprint Hydrolytically deficient MutS E694A is defective in the MutL-dependent activation of MutH and in the mismatch-dependent assembly of the MutS.MutL.heteroduplex complex
    Celia Baitinger
    Howard Hughes Medical Institute and Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:49505-11. 2003
    ..MutL.DNA ternary complex. Although a putative ternary complex can be observed in the presence of MutS E694A, assembly of this structure displays little if any dependence on a mismatched base pair...
  16. ncbi request reprint Assembly and molecular activities of the MutS tetramer
    Keith P Bjornson
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:34667-73. 2003
    ..Compared with native MutS, the ability of MutS800 to promote MutL-dependent activation of MutH is substantially reduced...
  17. pmc MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta
    Ravi R Iyer
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 285:11730-9. 2010
    ..These findings also indicate that MutSbeta- and MutSalpha-initiated repair events differ in fundamental ways...
  18. pmc A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair
    Farid A Kadyrov
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:8495-500. 2009
    ..Such a mechanism may account, at least in part, for the Exo1-independent repair that occurs in eukaryotic cells, and hence the modest cancer predisposition of Exo1-deficient mammalian cells...

Research Grants42

  1. ENZYMOLOGY OF EUKARYOTIC DNA MISMATCH REPAIR
    Paul Modrich; Fiscal Year: 1993
    ..Should a defect in mismatch repair be associated with the mammalian MutS deletion, the spontaneous mutabilities of wild type and mutant lines will be assessed...
  2. Enzymology and Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2003
    ..Consequently, the investigators will ask whether these two systems function in a coordinated manner to suppress illegitimate recombination events. ..
  3. Enzymology Of Eukaryotic Mismatch Repair
    PAUL LAWRENCE MODRICH; Fiscal Year: 2010
    ..abstract_text> ..
  4. MOLECULAR MECHANISM OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 2003
    ..They hope to establish the molecular composition of these complexes. This phase of the work will also address the basis of the specific requirement for DNA polymerase III holoenzyme in the repair synthesis step of the reaction. ..
  5. ENZYMOLOGY OF EUKARYOTIC DNA MISMATCH REPAIR
    Paul Modrich; Fiscal Year: 2002
    ..Should excision activities become available during the course of the project, the molecular studies will be extended to include these activities. ..
  6. MOLECULAR MECHANISMS OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 2007
    ..abstract_text> ..
  7. Enzymology Of Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2007
    ....
  8. Enzymology and Eukaryotic Mismatch Repair
    Paul Modrich; Fiscal Year: 2006
    ..Consequently, the investigators will ask whether these two systems function in a coordinated manner to suppress illegitimate recombination events. ..
  9. MOLECULAR MECHANISMS OF DNA-PROTEIN INTERACTION
    Paul Modrich; Fiscal Year: 1999
    ..Lastly, the applicant will explore "reagent applications" of mismatch repair activities for mutation detection and for fractionation of a population of DNA molecules, a subset of which may contain one or more mismatched base pairs. ..
  10. ENZYMATIC BASIS OF TYPE II RESTRICTION AND MODIFICATION
    Paul Modrich; Fiscal Year: 1980
    ..We are also pursuing work of the mechanism and biological function of the Escherichia coli dam methylase which is responsible for almost all 6-methyladenine residue in this organism...