CURRICULUM VITAE Paul L

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CURRICULUM VITAE Paul L. Modrich Department of Biochemistry Box 3711, Duke University Medical Center Durham, NC 27710 Tel (919) 684-2775, Fax (919) 681-7874, email pm11 at duke.edu

EDUCATION 1968 B.S., Biology, Massachusetts Institute of Technology 1973 Ph.D., Biochemistry, Stanford University (with I.R. Lehman) 1973-1974 Postdoctoral study, Biological Chemistry, Harvard University (with Charles Richardson)

ACADEMIC POSITIONS 2015 Professor of Chemistry, Duke University 1994-2019 Investigator, Howard Hughes Medical Institute 1989-1992 Director, Duke University Program in Genetics 1988 James B. Duke Professor of Biochemistry, Duke University 1984 Professor of Biochemistry, Duke University 1980 Associate Professor of Biochemistry, Duke University 1976 Assistant Professor of Biochemistry, Duke University 1974 Assistant Professor of Chemistry, University of California, Berkeley

PUBLIC SERVICE 2019-present Honorary Board, Society for Science & the Public 2017 HHMI Trustees presentation 2008 Co-Chair Nucleic Acids Gordon Research Conference 2004-present Editorial Committee, Annual Review of Biochemistry 2004-2005 General Motors Cancer Research Foundation Awards Assembly 2003-2008 Editorial Board, DNA Repair 2001 NIEHS Director review panel 2000-2008 Editorial Board, Proceedings of the National Academy of Sciences 1996-1997 NIEHS External Review Group 1995-2000 Board of Scientific Counselors, NIEHS 1989-1992, 1997-2000 Councilor, ASBMB 1995-1997 Publications Committee ASBMB, Chair 1996-97 1993-1995 DOE HERAC, Human Genome Subcommittee 1992-1994 Associate Editor, Biochemistry, 1992 - 1994 1986-1991, 1995-2003 Editorial Advisory Board Biochemistry 1982-1983 Editorial Board Journal Biological Chemistry 1981-1987 Visiting Committee on Biology to the MIT Corporation, 1980-1982 Editorial Board Nucleic Acids Research 1980-1984 NIH Biochemistry Study Section Paul L Modrich

HONORS AND AWARDS 2018 Honorary Doctorate, Tsinghua University, Beijing, China 2017 Gregor Mendel Medal, Masaryk University and St. Thomas Abbey 2017 Fellow, American Association for Cancer Research Academy 2016 Fellow, National Academy of Inventors 2016 North Carolina Award in Science 2016 Arthur Kornberg and Paul Berg Lifetime Achievement Award in Biomedical Sciences, Stanford Medicine Alumni Association 2016 Honorary Fellow, Royal Society of Chemistry 2015 Nobel Prize in Chemistry 2008 Duke Medical Alumni Distinguished Faculty Award 2007 Ohio State University Human Cancer Genetics Medal 2005 American Cancer Society Medal of Honor 2004 Fellow, American Academy of Arts and Sciences 2003 Fellow, American Academy of Microbiology 2003 Member, Institute of Medicine (now National Academy of Medicine) 2000 Feodor Lynen Medal 1999 Robert J. and Claire Pasarow Foundation Award in Cancer Research 1998 Fellow, American Association for the Advancement of Science 1996 General Motors Mott Prize in Cancer Research 1993 Member, National Academy of Sciences 1986 NIH MERIT Award 1983 Pfizer Award in Enzyme Chemistry, American Chemical Society 1977 Henry and Camille Dreyfus Teacher Scholar Award

HONORARY LECTURES 2019 Nobel Laureate Lecture, 11th ISABS Conference, Split Croatia 2018 Keynote Lecture, Frontiers in Cancer Science, Singapore 2018 Tsinghua Global Vision Lecture, Tsinghua University 2018 Keynote Lecture, icBEST meeting, Shenzhen, China 2018 Tushar K Chowdhury Lecture, University of Oklahoma Health Sciences Center 2017 Norman Davidson Lecture, Caltech 2017 Mendel Lecture, Masaryk University & St Thomas Abbey, Brno Czech Republic 2017 Nobel Laureate Lecture, Dresden Technical University 2017 Whitten Lecture, University of North Carolina, Chapel Hill 2017 Stanley Cohen Frontiers of Biochemistry Lecture, Vanderbilt University 2016 NIEHS Distinguished Lecture 2016 Wogan Lecture, M.I.T. 2016 Keynote Lecture, Howard Hughes Medical Institute 2016 Keynote Lecture, Environmental Mutagenesis and Genomics Society annual meeting 2016 Pioneering Biological Discovery Seminar, University of Texas Medical Branch 2015 Chemistry Nobel Prize Lecture 2014 Keynote lecture, US-EU Conference on Repair of Endogenous DNA Damage 2010 Lawrence Grossman Lectureship, Johns Hopkins Bloomberg School of Public Health 2007 Keynote lecture M. D. Anderson Lost Pines Conference 2004 Distinguished Speaker in Molecular and Cellular Biology, University of Illinois Urbana 2001 University Lecture, University of Texas Southwestern Medical Center 2001 Dean's Lecture, University of Kentucky 2000 Lynen Lecture, Miami Winter Symposium

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2000 Keynote Lecture, American Association for Cancer Research Meeting on DNA Repair 1999 Kelsey Lecture, Texas A & M Institute for Bioscience and Technology 1999 Distinguished Lecturer in Pharmacology, St. Jude Childrens Hospital 1999 Herriot Lecture, Johns Hopkins University School of Medicine 1999 Garrard Lectureship, Oklahoma Medical Research Foundation 1998 Keynote Lecture, University of Chicago Cell Proliferation and Cancer Biology Symposium 1998 Distinguished Lecture, National Institute of Environmental Health Sciences 1995 University Lecture, University of Texas Southwestern Medical Center 1995 Frontiers in Science Lecture, National Institute of Environmental Health Sciences 1995 Wellcome Lecturer, UCSB

RESEARCH SUPPORT Ongoing Research Support

No number Modrich (PI) 12/1/2019 - 10/31/2021 Howard Hughes Medical Institute The Howard Hughes Medical Institute provided a gift to Duke University for use by P. Modrich as he winds down his research program.

Completed Research Support

No number Modrich (PI) 6/1/1994 - 10/31/2019 Howard Hughes Medical Institute The Howard Hughes Medical Institute provided general support for the operations of our laboratory. These funds, which were allocated annually, were not directed to a particular project but rather provided my salary and a support base for the entire research group.

R01 GM45190 Modrich (PI) 4/1/1992 - 2/28/2019 NIH/NIGMS Enzymology of Eukaryotic Mismatch Repair: These studies established molecular features of mismatch repair in human cells, documented inactivation of the pathway in Lynch syndrome and certain sporadic cancer cells, clarified its involvement in DNA damage signaling, and provided potential molecular insight into its mode of action in (CAG)n/(CTG)n triplet repeat expansion.

P01 CA092584-01 Tainer/Coope r (PI) 9/1/2001 - 8/31/2016 Subproject 5 Mismatch repair interactions, Modrich Project Leader NIH/NCI Structural Cell Biology of DNA Repair Machines, Subproject 5. This Subproject, which also involved the laboratories of L. Beese (Duke University) and R. Kolodner (UC San Diego), addressed the structural nature of human and yeast mismatch repair proteins, as well as structural analysis of multi-protein mismatch repair complexes.

PCM76-04914 & PCM78-23036 Modrich (PI) 11/1/1976 -6/30/1982 NSF Role of subunits in T7 polymerase activity. This project addressed the functional roles of viral- and host-specified subunits in phage T7 DNA polymerase.

R01 GM23719 Modrich (PI) 8/1/1974 - 7/31/2008 NIH/NIGMS (Grant number changed from GM21610 upon move from Berkeley to Duke in July 1976)

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Molecular Mechanisms of DNA-Protein Interaction: These studies addressed the nature of DNA search and specific site recognition by EcoRI enzymes and established basic molecular features of the E. coli DNA mismatch repair system.

PUBLICATIONS

1. Modrich, P. and Lehman, I.R. (1970) A simple and rapid assay of polynucleotide joining (ligase) activity by measurement of circle formation from linear deoxyadenylate-deoxythymidylate copolymer, J. Biol. Chem. 245, 3626-3631.

2. Modrich, P. and Lehman, I.R. (1971) Enzymatic characterization of a mutant of Escherichia coli with an altered DNA ligase, Proc. Natl. Acad. Sci. U. S. A. 68, 1002-1005.

3. Modrich, P., Lehman, I.R. and Wang, J.C. (1972) Reversal of Escherichia coli deoxyribonucleic acid ligase reaction, J. Biol. Chem. 247, 6370-6372.

4. Modrich, P., Anraku, Y., and Lehman, I.R. (1973) Deoxyribonucleic acid ligase: Isolation and physical characterization of the homogeneous enzyme from Escherichia coli, J. Biol. Chem. 248, 7495-7501.

5. Modrich, P. and Lehman, I.R. (1973) Deoxyribonucleic acid ligase: A steady state kinetic analysis of the reaction catalyzed by the enzyme from Escherichia coli, J. Biol. Chem. 248, 7502-7511.

6. Konrad, E.B., Modrich, P. and Lehman, I.R. (1973) Genetic and enzymatic characterization of a mutant of Esherichia coli K12 with a temperature sensitive DNA ligase, J. Mol. Biol. 77, 519-529.

7. Konrad, E.B., Modrich, P. and Lehman, I.R. (1974) DNA synthesis in strains of Escherichia coli K12 with temperature-sensitive DNA ligase and DNA polymerase I, J. Mol. Biol. 90, 115-126.

8. Modrich, P. and Richardson, C.C. (1975) Bacteriophage T7 DNA polymerase: An enzyme composed of phage and host-specified subunits, J. Biol. Chem. 250, 5515-5522.

9. Modrich, P. and Richardson, C.C. (1975) A protein of Escherichia coli required for bacteriophage T7 DNA polymerase activity, J. Biol. Chem. 250, 5508-5514.

10. Panasenko, S.M., Modrich, P. and Lehman, I.R. (1976) Modification of Escherichia coli DNA ligase by cleavage with trypsin, J. Biol. Chem. 251, 3432-3435.

11. Modrich, P. and Zabel, D. (1976) EcoRI endonuclease; Physical and catalytic properties of the homogeneous enzyme, J. Biol. Chem. 251, 5866-5874.

12. Rubin, R.A. and Modrich, P. (1977) EcoRI methylase: Physical and catalytic properties of the homogeneous enzyme, J. Biol. Chem. 252, 7265-7272.

13. Modrich, P. and Rubin, R.A. (1977) Role of the 2-amino group of deoxyguanosine in sequence recognition by EcoRI restriction and modification enzymes, J. Biol. Chem. 252, 7273-7278.

14. Rubin, R.A. and Modrich, P. (1978) Substrate dependence of the mechanism of EcoRI endonuclease, Nucleic Acids Res. 5, 2991-2997.

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15. Adler, S. and Modrich, P. (1979) T7-induced DNA polymerase: Characterization of associated exonuclease activities and resolution into biologically active subunits, J. Biol. Chem. 254, 11605-11614.

16. Geier, G.E. and Modrich, P. (1979) Recognition sequence of the dam methylase of Escherichia coli K12 and mode of cleavage of DpnI endonuclease, J. Biol. Chem. 254, 1408-1413.

17. Modrich, P. (1979) Structures and mechanisms of DNA restriction and modification enzymes, Quart. Rev. Biophys. 12, 315-369.

18. Rubin, R.A. and Modrich, P. (1980) Purification and properties of EcoRI endonuclease, Methods in Enzymology, 65, part I, 96-104.

19. Clark, D., Lightner, V., Edgar, R., Modrich, P., Cronan, J.E., and Bell, R.M. (1980) Regulation of phospholipid biosynthesis in Escherichia coli: Cloning of the structural gene for the biosynthetic sn-glycerol-3-phosphate dehydrogense, J. Biol. Chem. 255, 714-717.

20. Lightner, V.A., Larson, T.J., Tailleur, P., Kantor, G.D., Raetz, C.R.H., Bell, R.M. and Modrich, P. (1980) Membrane phospholipid synthesis in Eshcerichia coli: Cloning of a structural gene (plsB) of the sn-glycerol- 3-phosphate acyltransferase, J. Biol. Chem., 255, 9413-9420.

21. Larson, T.J., Lightner, V.A., Green, P.R., Modrich, P. and Bell, R.M. (1980) Membrane phospholipid synthesis in Eshcerichia coli: Identification of the sn-glycerol-3-phosphate acyltransferase polypeptide as the plsB gene product, J. Biol. Chem., 255, 9421-9426.

22. Jack, W.E., Rubin, R.A., Newman, A. and Modrich, P. (1981) Structures and mechanisms of EcoRI DNA restriction and modification enzymes. In Gene Amplification and Analysis Vol I: Restriction Endonucleases J.G. Chirikjian, Ed., Elsevier-North Holland.

23. Herman, G.E. and Modrich, P. (1981) Escherichia coli K12 clones that overproduce dam methylase are hypermutable, J. Bact. 145, 644-646.

24. Young, T.S., Modrich, P., Beth, A., Jay, E. and Kim, S.H. (1981) Preliminary X-ray diffraction studies of EcoRI restriction endonuclease-DNA complex, J. Mol. Biol. 145, 607-610.

25. Newman, A.K., Rubin, R.A., Kim, S.H., and Modrich, P. (1981) DNA sequences of structural genes for EcoRI DNA restriction and modification enzymes, J. Biol. Chem. 256, 2131-2139.

26. Rubin, R.A., Modrich, P. and Vanaman, T.C. (1981) Partial NH2- and COOH terminal sequence analysis of EcoRI DNA restriction and modification enzymes, J. Biol. Chem. 256, 2140-2142.

27. Lu, A.-L., Jack, W.E., and Modrich, P. (1981) DNA determinants important in sequence recognition by EcoRI endonuclease, J. Biol. Chem. 256, 13200-13206.

28. Bowden, D.W. and Modrich, P. (1981) In vitro studies on the bacteriophage P2 terminase system, In Bacteriophage Assembly, Alan R. Liss, NY, NY, pp 223-230.

29. Herman, G.E. and Modrich, P. (1982) Escherichia coli dam methylase: Physical and catalytic properties of the homogeneous enzyme, J. Biol. Chem. 257, 2605-2612.

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30. Modrich, P. (1982) Studies on sequence recognition by Type II restriction and modification enzymes, CRC Critical Reviews in Biochemistry 13, 287-323.

31. Brody, R.S., Adler, S., Modrich, P., Stec, W.J., Leznikowski, Z.J. and Frey, P.A. (1982) The stereochemical course of nucleotidyl transfer catalyzed by bacteriophage T7-induced DNA polymerase, Biochemistry, 21, 2570-2572.

32. Jack, W.E., Terry, B.J., and Modrich, P. (1982) Involvement of outside DNA sequences in the major kinetic path by which EcoRI endonuclease locates and leaves its recognition sequence, Proc. Natl. Acad. Sci. U. S. A. 79, 4010-4014.

33. Modrich, P. and Roberts, R.J. (1982) Type II restriction and modification enzymes, in The Nucleases, eds. S. M. Linn and R. J. Roberts, Cold Spring Harbor, pp. 109-154.

34. Cheng, S.-C. and Modrich, P. (1983) A positive selection cloning vehicle useful for overproduction of hybrid proteins, J. Bact. 154, 1005-1008.

35. Adler, S. and Modrich, P. (1983) T7-induced DNA polymerase: Requirement for thioredoxin sulfhydryl groups, J. Biol. Chem. 258, 6956-6962.

36. Pukkila, P. J., Peterson, J., Herman, G., Modrich, P. and Meselson, M. (1983) Effects of high levels of DNA adenine methylation on methyl-directed mismatch repair in E. coli, Genetics 104, 571-582.

37. Lightner, V.A., Bell, R.M., and Modrich, P. (1983) The DNA sequence encoding the plsB and dgk loci of Escherichia coli, J. Biol. Chem. 258, 10856-10861.

38. Green, P.R., Vanaman, T.C., Modrich, P. and Bell, R.M. (1983) Partial NH2- and COOH-terminal sequence and cyanogen bromide peptide analysis of Escherichia coli sn-glycerol-3-phosphate acyltransferase, J. Biol. Chem. 258, 10862-10866.

39. Lu, A.-L., Clark, S., and Modrich, P. (1983) Methyl-directed repair of DNA base pair mismatches in vitro, Proc. Natl. Acad. Sci. U. S. A. 80, 4639-4643.

40. Terry, B.J., Jack, W.E., Rubin, R.A., and Modrich, P. (1983) Thermodynamic parameters governing interaction of EcoRI Endonuclease with specific and nonspecific DNA sequences, J. Biol. Chem. 258, 9820- 9825.

41. Cheng, S.-C., Kim. R., King, K., Kim, S.-H., and Modrich, P. (1984) Isolation of gram quantities of EcoRI restriction and modification enzymes from an overproducing strain, J. Biol. Chem. 259, 11571-11575.

42. Manavalan, P., Johnson, W.C., and Modrich, P. (1984) Prediction of secondary and tertiary folds for EcoRI restriction endonuclease, J. Biol. Chem. 259, 11666-11667.

43. Kim, R., Modrich, P. and Kim, S.-H. (1984) Interactive recognition in EcoRI restriction enzyme-DNA complex, Nucleic Acids. Res. 12, 7285-7292.

44. Lu, A.-L., Welsh, K., Clark, S., Su, S. and Modrich, P. (1984) Repair of DNA base pair mismatches in extracts of Escherichia coli, Cold Spring Harbor Symp. Quant. Biol. 49, 589-596.

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45. Cheng, S.-C., Herman, G. and Modrich, P. (1985) Extent of equilibrium perturbation of the DNA helix upon enzymatic methylation of adenine residues, J. Biol. Chem. 260, 191-194.

46. Bowden, D.W. and Modrich, P. (1985) In vitro maturation of circular bacteriophage P2 DNA:Purification of ter components and characterization of the reaction, J. Biol. Chem. 260, 6999-7007.

47. Terry, B.J., Jack, W.E., and Modrich, P. (1985) Facilitated diffusion during catalysis by EcoRI endonuclease, J. Biol. Chem. 260, 13130-13137.

48. Modrich, P. (1986) Mismatch Correction in Mechanisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment (eds. M. G. Simic, L. Grossman and A. D. Upton), pp. 303-310, Plenum Press, New York.

49. Su, S.-S. and Modrich, P. (1986) Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs, Proc. Natl. Acad. Sci. U. S. A. 83, 5057-5061.

50. Lahue, R.S., Su, S.-S., Welsh, K. and Modrich, P. (1987) Analysis of methyl-directed mismatch repair in vitro, UCLA Symp. Mol. Cell. Biol. 47, 125-134.

51. Terry, B.J., Jack, W.E., and Modrich, P. (1987) Mechanism of specific site location and DNA cleavage by EcoRI endonuclease. In Gene Amplification and Analysis, Vol V: Restriction Endonucleases II, (J.G. Chirikjian, Ed.), pp. 103-118, Elsevier Science Publishing Co, New York, NY.

52. Lahue, R.S., Su., S.-S., and Modrich, P. (1987) Requirement for d(GATC) sequences in Escherichia coli mutHLS mismatch correction, Proc. Natl. Acad. Sci. U. S. A., 84, 1482-1486.

53. Modrich, P. (1987) DNA mismatch correction, Ann. Rev. Biochem. 56, 435-466.

54. Rebbe, N.F., Ware, J., Bertina, R.M., Modrich, P. and Stafford, D.W. (1987) Nucleotide sequence of a cDNA for a member of the human 90-kDa heat shock protein family, Gene 53, 235-245.

55. Welsh, K.M., Lu, A-L., Clark, S., and Modrich, P. (1987) Isolation and characterization of the Escherichia coli mutH gene product, J. Biol. Chem. 262, 15624-15629.

56. Lahue, R. S. and Modrich, P. (1987) Methyl-directed mismatch repair in Escherichia coli, Mutat. Res. 198, 37-43.

57. Jhon, N.-I., Casas-Finet, J.R., Maki, A.H., and Modrich, P. (1988) Investigation of the complexes of EcoRI endonuclease with decanucleotides containing canonical and modified recognition sequences using fluorescence and optical detection of magnetic resonance spectroscopy, Biochim. Biophys. Acta 949, 189- 194.

58. Su, S.-S., Lahue, R.S., Au, K.G., and Modrich, P. (1988) Mispair specificity of methyl-directed DNA mismatch correction in vitro, J. Biol. Chem. 263, 6829-6835.

59. Jiricny, J., Su, S.-S., Wood, S. G., and Modrich, P. (1988) Mismatch-containing oligonucleotide duplexes bound by the E. coli mutS-encoded protein, Nucleic Acids Res. 16, 7843-7853.

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60. Au, K. G., Cabrera, M., Miller, J. H., and Modrich, P. (1988) Escherichia coli mutY gene product is required for specific A-G to C-G mismatch correction, Proc. Natl. Acad. Sci. U. S. A. 85, 9163-9166.

61. Su, S.-S., Grilley, M., Thresher, R., Griffith, J., and Modrich, P. (1989) Gap formation is associated with methyl-directed mismatch correction under conditions of restricted DNA synthesis, Genome 31, 104-111.

62. Grilley, M., Welsh, K. M., Su, S.-S., and Modrich, P. (1989) Isolation and characterization of the Escherichia coli mutL gene product, J. Biol. Chem. 264, 1000-1004.

63. Modrich, P. (1989) Methyl-directed DNA mismatch correction, J. Biol. Chem. 264, 6597-6600.

64. King, K., Benkovic, S. and Modrich, P. (1989) Glu-111 is required for activation of the DNA cleavage center of EcoRI endonuclease, J. Biol. Chem. 264, 11807-11815.

65. Wright, D., King, K. and Modrich, P. (1989) The negative charge of Glu-111 is required to activate the cleavage center of EcoRI endonuclease, J. Biol. Chem. 264, 11816-11821.

66. Lahue, R. S., Au, K. G., and Modrich, P. (1989) DNA mismatch correction in a defined system, Science, 245, 160-164.

67. Au, K. G., Clark, S., Miller, J. H., and Modrich, P. (1989) Escherichia coli mutY gene encodes an adenine glycosylase active on G-A mispairs, Proc. Natl. Acad. Sci. U. S. A. 86, 8877-8881.

68. Grilley, M., Holmes, J., Yashar, B., and Modrich, P. (1990) Mechanisms of DNA mismatch correction, Mutat. Res. 236, 253-267.

69. Holmes, J., Clark, S. and Modrich, P. (1990) Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines, Proc. Natl. Acad. Sci. U. S. A. 87, 5837-5841.

70. Modrich, P. (1991) Mechanisms and biological effects of mismatch repair, Annu. Rev. Genet. 25, 229-253.

71. Au, K. G., Welsh, K. and Modrich, P. (1992) Initiation of methyl-directed mismatch repair, J. Biol. Chem. 267 12142-12148.

72. Nelson, S. F., McCusker, J. H., Sander, M. A., Kee, Y., Modrich, P. and Brown, P. O. (1993) Genomic mismatch Scanning: A new approach to genetic linkage mapping, Nature Genetics 4, 11-18.

73. Naegeli, H., Modrich, P. and Friedberg, E. C. (1993) The DNA helicase activities of Rad3 protein of Saccharomyces cerevisiae and helicase II of Escherichia coli are differentially inhibited by covalent and non- covalent DNA modifications, J. Biol. Chem. 268, 10386-10392.

74. Cooper, D.L., Lahue R. S. and Modrich, P. (1993) Methyl-directed mismatch repair is bidirectional, J. Biol. Chem. 268, 11823-11829.

75. Grilley, M., Griffith, J., and Modrich, P. (1993) Bidirectional excision in methyl-directed mismatch repair, J. Biol. Chem. 268, 11830-11837.

76. Fang, W.-h. and Modrich, P. (1993) Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction, J. Biol. Chem. 268, 11838-11844.

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77. Kat, A., Thilly, W., Fang, W.-h., Longley, M., Li, G.-M., and Modrich, P. (1993) An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 90, 6424-6428.

78. Humbert, O., Prudhomme, M., Dowson, C. G., Modrich, P., and Claverys, J.-P. (1993) Hex-mediated generalized mismatch repair during transformation in Streptococcus pneumoniae, in DNA Transfer and Gene Expression in Microorganisms (eds. E. Balla, G. Berencsi, A. Szentirmai ), pp. 23-35, Intercept Ltd, Andover.

79. Fang, W.-h., Li, G.-m., Longley, M., Holmes, J., Thilly, W., and Modrich, P. (1993) Mismatch repair and genetic stability in human cells, Cold Spring Harbor Symp. Quant. Biol. 58, 597-603.

80. Hsieh, J.-C., Zinnen, S. and Modrich, P. (1993) Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase, J. Biol. Chem. 268, 24607-24613.

81. Parsons, R., Li, G.-M., Longley, M. J., Fang, W.-h., Papadopoulos, N., Jen, J., de la Chapelle, A., Kinzler, K.W., Vogelstein, B. and Modrich, P. (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells, Cell 75, 1227-1236.

82. Worth, L., Clark, S., Radman, M., and Modrich, P. (1994) Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs, Proc. Natl. Acad. Sci. U. S. A. 91, 3238-3241.

83. Zinnen, S., Hsieh, J.-C., and Modrich, P. (1994) Misincorporation and mispaired primer extension by human immunodeficiency virus reverse transcriptase, J. Biol. Chem. 269, 24195-24202.

84. Modrich, P. (1994) Mismatch repair, genetic stability, and cancer, Science 266, 1959-1960.

85. Modrich, P. (1995) Mismatch repair, genetic stability, and tumor avoidance, Phil. Trans. Royal Soc. B 347, 89-95.

86. Li, G.-M. and Modrich, P. (1995) Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs, Proc. Natl. Acad. Sci. U. S. A. 92, 1950-1954.

87. Modrich, P. (1995) A human protein with antimutator activity, Jap. J. Cancer Res., cover article.

88. Parsons, R., Li, G.-M., Longley, M., Modrich, P., Liu, B., Berk, T., Hamilton, S. R., Kinzler, K. W., and Vogelstein, B. (1995) Mismatch repair deficiency in phenotypically normal human cells, Science 268, 738- 740.

89. Drummond, J. T., Li, G.-M., Longley, M. J., and Modrich, P. (1995), Isolation of an hMSH2•p160 heterodimer that restores DNA mismatch repair to tumor cells, Science 268, 1909-1912.

90. Dong, Q., Barsky, D., Colvin, M. E., Melius, C. F., Ludeman, S. M., Moravek, J. F., Colvin, O. M., Bigner, D. D., Modrich, P., and Friedman, H. S. (1995) A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC), Proc. Natl. Acad. Sci. U. S. A. 92, 12170-12174

91. Modrich, P. and Lahue, R. (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology, Ann. Rev. Biochem. 65, 101-133.

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92. Eshleman, J. R., Markowitz, S. D., Donover, P. S., Lang, E. Z., Lutterbaugh, J. D., Li, G.-M., Longley, M., Modrich, P., Veigl, M. L., and Sedwick, D. (1996) Diverse hypermutability of multiple expressed sequence motifs present in cancer with microsatellite instability, Oncogene 12, 1425-1432.

93. Smith, J. and Modrich, P. (1996) Mutation detection with MutH, MutL, and MutS mismatch repair proteins, Proc. Natl. Acad. Sci. U. S. A. 93, 4374-4379.

94. Iaccarino, I., Palombo, F., Drummond, J., Truong, O., Hsuan, J. J., Modrich, P., and Jiricny, J. (1996) MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as a heterodimer with MSH2, Current Biol. 6, 484-486.

95. Duckett, D. R., Drummond, J. T., Murchie, A. I. H., Reardon, J. T., Sancar. A., Lilley, D. M. J., and Modrich, P. (1996) Human MutSa recognizes damaged DNA base pairs containing O6-methylguanine, O4- methylthymine or the cisplatin-d(GpG) adduct, Proc. Natl. Acad. Sci. U. S. A. 93, 6443-6447.

96. Drummond, J. T., Anthoney, A., Brown, R., and Modrich, P. (1996) Cisplatin and Adriamycin resistance are associated with MutLa and mismatch repair deficiency in an ovarian tumor cell line, J. Biol. Chem. 271, 19645-19648.

97. Allison, D. P., Kerper, P. S., Doktycz, M. J., Spain, J. A., Modrich, P., Larimer, F. W., Thundat, T., and Warmack, R. J. (1996) Direct atomic force microscope imaging of EcoRI endonuclease site specifically bound to plasmid DNA molecules, Proc. Natl. Acad. Sci. U. S. A. 93, 8826-8829.

98. Mu, D., Mihray, T., Duckett, D. R., Drummond, J. T., Modrich, P., and Sancar, A. (1997) Recognition and repair of compound DNA lesions (base damage/mismatch) by human mismatch repair and excision repair systems, Mol. Cell. Biol. 17, 760-769.

99. Longley, M. J., Pierce, A. J., and Modrich, P. (1997) DNA polymerase is required for human mismatch repair in vitro, J. Biol. Chem. 272, 10917-10921.

100. Allison, D. P., Kerper, P. S., Doktycz, M. J., Thundat, T., Modrich, P., Larimer, F. W., Johnson, D. K., Hoyt, P. R., Mucenski, M. L., and Warmack, R. J. (1997) Mapping individual cosmid DNAs by direct AFM imaging, Genomics 41, 379-384.

101. Smith, J. and Modrich, P. (1997) Removal of polymerase-produced mutant sequences from PCR products, Proc. Natl. Acad. Sci. U. S. A. 94, 6847-6850.

102. Allen, D. J., Makhov, A, Grilley, M., Taylor, J., Thresher, R., Modrich, P., and Griffith, J. D., (1997) MutS mediates heteroduplex loop formation by a translocation mechanism, EMBO J. 16, 4467-4476.

103. Friedman, H. S., Johnson, S., Dong, Q., Schold, S. C., Rasheed, A., Bigner, S., Ali-Osman, F. Dolan, E., Colvin, O. M., Houghton, P., Germaine, G., Drummond, J. T., Keir, S., Marcelli, S., Bigner, D., and Modrich, P. (1997) Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft, Cancer Res. 57, 2933-2936.

104. Modrich, P. (1997) Mismatch repair: The trek from E. coli to human cells, In Accomplishments in Cancer Research 1996, ed. J. G. Fortner & P. A. Sharp, Lippincott-Raven, NY, 72-83.

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105. Modrich, P. (1997) Strand-specific mismatch repair in mammalian cells, J. Biol. Chem. 272, 24727-24730.

106. Drummond, J. T., Genschel, J., Wolf, E., and Modrich, P. (1997) DHFR/MSH3 amplification in methotrexate- resistant cells alters the hMutSa:hMutSb ratio and reduces the efficiency of base-base mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 94, 10144-10149.

107. Nicolaides, N. C., Littman, S., Modrich, P., Kinzler, K. W., and Vogelstein, B. (1998) A naturally-occurring hPMS2 mutation can confer a dominant negative mutator phenotype, Mol. Cell. Biol. 18, 1635-1641.

108. Eshleman, J. R., Donover, P. S., Littman, S. J., Swinler, S. E., Li, G.-M., Lutterbaugh, J. D., Willson, J. K. V., Modrich, P., Sedwick, W. D., Markowitz, S. D., and Veigl, M. L. (1998) Increased transversions in a novel mutator colon cancer, Oncogene 16, 1125-1130.

109. Yamaguchi, M., Dao, V., and Modrich, P. (1998) MutS and MutL activate DNA helicase II in a mismatch- dependent manner, J. Biol. Chem. 273, 9197-9201.

110. Dao, V. and Modrich, P. (1998) Mismatch, MutS, MutL, and helicase II-dependent unwinding from the single-strand break of an incised heteroduplex, J. Biol. Chem. 273, 9202-9207.

111. Lee, S. E., Johnson, S. P., Hale, L. P., Ni, J., Bullock, N., Fuchs, H., Friedman, A., McLendon, R., Bigner, D. D., Modrich, P., and Friedman, H. S. (1998) Analysis of DNA mismatch repair proteins in human medulloblastoma, Clin. Cancer Res, 4, 1415-1419.

112. Genschel, J., Littman, S. J., Drummond, J. T., and Modrich P. (1998) Isolation of hMutSb from human cells and comparison of the mismatch specificities of hMutSb and hMutSa, J. Biol. Chem. 273, 19895-19901.

113. Veigl, M. L., Kasturi, L., Olechnowicz, J., Ma, A., Lutterbaugh, J. D., Periyasamy, S., Li, G.-M., Drummond, J., Modrich, P., Sedwick, W. D., and Markowitz, S. D. (1998) Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers, Proc. Natl. Acad. Sci. U. S. A. 95, 8698- 8702.

114. Hanley, M. L., Elion, G. B., Colvin, O. M., Modrich, P. L., Keir, S., Adams, D. J., Bigner, D. D., Friedman, H. S. (1998) Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors, Cancer Chemother. Pharmacol. 42, 479-482.

115. Friedman, H. S., Kerby, T. A., Dugan, M., McLendon, R. E., Bigner, S. H., Henry, A. J., Ashley, D., Krischer, J., Lovell, S., Rasheed, K., Marchev, F., Marchev, F., Semen, A. J., Cokgor, I., Rich, J., Stewart, E., Colvin, M., Provenzale, J. M., Bigner, D. D., Haglund, M., Longee, D., Bottom, K., Friedman, A. H., and Modrich, P. (1998) DNA mismatch repair and O6-alkylguanine-DNA alkytransferase analysis and response to Temodal® in newly diagnosed malignant glioma, J. Clin. Oncol. 16, 3851-3857.

116. Blackwell, L., Bjornson, K., and Modrich, P. (1998) DNA-Dependent activation of the hMutSa ATPase, J. Biol. Chem. 273, 32049-32054.

117. Blackwell, L, Martik, D., Bjornson, K., Bjornson, E., and Modrich, P. (1998) Nucleotide-promoted release of hMutSa from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism, J. Biol. Chem. 273, 32055-32062.

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118. Dong, Q., Johnson, S. P., Colvin, O. M., Bullock, N., Kilborn, C., Runyon, G., Sullivan, D., Easton, J., Bigner, D. D., Modrich, P., and Friedman, H. S. (1999) Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 MED(4-HC), Cancer Chemother. Pharmacol, 43, 73-79.

119. Friedman, H. S., Pegg. A. E., Johnson, S. P., Loktionova, N. A., Dolan, M. E., Modrich, P., Moschel, R. C., Struck, R., Brent, T. P., Ludeman, S., Bullock, N., Kilborn, C., Keir, S., Dong, Q., Bigner, D. D., and Colvin, O. M (1999) Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkytransferase, Cancer Chemother. Pharmacol, 43, 80-85.

120. Littman, S. J., Fang, W.-h., and Modrich, P. (1999) Repair of large insertion/deletion heterologies in human nuclear extracts is directed by a 5' single-strand break and is independent of the mismatch repair system, J. Biol. Chem. 274, 7474-7481.

121. Wright, D. J., Jack, W. E., and Modrich, P. (1999) The kinetic mechanism of EcoRI endonuclease, J. Biol. Chem. 274, 31896-31902.

122. Duckett, D. R., Bronstein, S. M., Taya, Y., and Modrich, P. (1999) hMutSa- and hMutLa-dependent phosphorylation of p53 in response to DNA methylator damage, Proc. Natl. Acad. Sci. U. S. A. 96, 12384- 12388.

123. Hoyt, P. R., Doktycz, M. J., Modrich, P., Warmack, R. J., and Allison, D. P. (2000) Identifying sequence similarities between DNA molecules, Ultramicroscopy 82, 237-244.

124. Bjornson, K. P., Allen, D. J., and Modrich, P. (2000) Modulation of MutS ATP hydrolysis by DNA cofactors, Biochemistry, 39, 3176-3183.

125. Spampinato, C. and Modrich, P. (2000) The MutL ATPase is required for mismatch repair, J. Biol. Chem. 275, 9863-9869.

126. Ma, A.-H., Xia, L., Littman, S. J., Swinler, S., Lader, G., Polinkovsky, A., Olechnowicz, J., Kasturi, L., Lutterbaugh, J., Modrich, P., Beigl, M. L., Markowitz, S. D., Sedwick, W. D. (2000) Somatic mutation of hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability, Oncogene 19, 2249-2256.

127. Burdett, V., Baitinger, C., Viswanathan, M., Lovett, S., and Modrich, P. (2001) In vivo requirement for RecJ, ExoVII, ExoI and ExoX in methyl-directed mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 98, 6765-6770.

128. Viswanathan, M., Burdett, V., Baitinger, C., Modrich, P., and Lovett, S. (2001) Redundant exonuclease involvement in Escherichia coli methyl-directed mismatch repair, J. Biol. Chem. 276, 31053-31058.

129. Blackwell, L. J., Wang, S., and Modrich, P. (2001) DNA chain length dependence of formation and dynamics of hMutSa•hMutLa•heteroduplex complexes, J. Biol. Chem. 276, 33233-33240.

130. Blackwell, L. J., Bjornson, K. P., Allen, D. J., and Modrich P. (2001) Distinct MutS DNA binding modes that are differentially modulated by ATP binding and hydrolysis, J. Biol. Chem. 276, 34339-34347.

131. Chen, S., Bigner, S. H., and Modrich, P. (2001) High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6, Proc. Natl. Acad. Sci. U. S. A. 98, 13802-13807.

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132. Genschel, J., Bazemore, L. R., and Modrich, P. (2002) Human Exonuclease I is Required for 5' and 3' Mismatch Repair, J. Biol. Chem. 277, 13302-13311.

133. Bacolod, M. D., Johnson, S. P., Ali-Osman, F., Modrich, P., Bullock, N. S., Colvin, O. M., Bigner, D. D. and Friedman, H. S. (2002) Mechanisms of resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea in human medulloblastoma and rhabdomyosarcoma, Mol. Cancer Ther. 1, 727-736.

134. Bjornson, K. P. and Modrich, P. (2003) Differential and simultaneous adenosine di- and triphsophate binding by MutS, J. Biol. Chem. 278, 18557-18562.

135. Bjornson, K. P., Sage, H., Blackwell, L. J., Baitinger, C., Allen, D., and Modrich, P. (2003) Assembly and Molecular Activities of the MutS Tetramer, J. Biol. Chem., 278, 34667-34673.

136. Genschel, J. and Modrich, P. (2003) Mechanism of 5'-directed excision in human mismatch repair, Mol. Cell 12, 1077-1086.

137. Baitinger, C., Burdett, V. and Modrich, P. (2003) 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, J. Biol. Chem. 278, 49505-49511.

138. Yang Q., Zhang R., Wang X. W., Linke S. P., Sengupta, S., Hickson I. D., Littman S. J., Modrich P., and Harris C. C. (2004) The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase in homologous DNA recombination, Oncogene 23, 3749-3756.

139. Martik, D., Baitinger, C. and Modrich, P. (2004) Differential Specificities and Simultaneous Occupancy of Human MutSa Nucleotide Binding Sites, J. Biol. Chem. 279, 28402-28410.

140. Velinchik, M., Solit, D., Basso, A., Huezo, H., Lucas, B., He, H., Spampinato, C., Modrich, P., Rosen, N., and Chiosis, G. (2004) Targeting wide-range oncogenic transformation via PU24FC1, a specific inhibitor of tumor Hsp90, Chem. & Biol. 11, 787-797.

141. Dzantiev, L., Constantin, N., Genschel, J., Iyer, R. R., Burgers, P. M., and Modrich, P. (2004) A Defined Human System That Supports Bidirectional Mismatch-Provoked Excision, Mol. Cell, 15, 31-41.

142. Bacolod, M. D., Johnson, S. P., Pegg, A. E., Dolan, M. E., Moschel, R. C., Bullock, N. S., Fang, Q., Colvin, O. M., Modrich, P., Bigner, D. D., Friedman, H. S. (2004) Brain tumor cell lines resistant to O6- benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O6-alkylguanine-DNA alkyltransferase mutations, Mol. Cancer. Ther. 3, 1127-1135

143. Modrich, P. (2005) Early thinking on the nature of mismatch repair, DNA Repair 4, 103-131.

144. Cheng, C. L., Johnson, S. P., Keir, S. T., Quinn, J. A., Ali-Osman, F., Szabo, C., Li, H., Salzman, A. L., Dolan, M. E., Modrich, P., Bigner, D. D., and Friedman, H. S. (2005) Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft, Mol. Cancer Ther. 4, 1364-1368

145. Koshiji, M., To, K. K. W., Hammer, S. Kumamoto, K., Harris, A. L., Modrich, P. and Huang, L. E. (2005) HIF- 1a induces genetic instability by transcriptionally down regulating MutSa expression, Mol. Cell 17, 793-

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803.

146. Genschel, J. and Modrich, P. (2005) Analysis of the excision step in human DNA mismatch repair, Methods Enzymol. 408 part A, 273-284.

147. Constantin, N., Dzantiev, L., Kadyrov, F. A., and Modrich P. (2005) Human mismatch repair: reconstitution of a nick-directed bidirectional reaction, J. Biol. Chem. 280, 39752-39761, PMCID: PMC1435381.

148. Iyer, R. R., Pluciennik, A., Burdett, V., and Modrich, P. L. (2006) Mismatch repair: functions and mechanisms, Chem. Rev. 106, 302-323.

149. Baker, D., Church, G., Collins, J., Endy, D., Jacobson, J., Keasling, J., Modrich, P., Smolke, C. and Weiss, R. (2006) Engineering life: building a FAB for Biology, Scientific American, 294, 44-51.

150 Chintagumpala, M. M., Friedman, H. S., Stewart, C. F., Kepner, J., McLendon, R. E., Modrich, P. L., McCluggage, C., Burger, P., Holmes, E., Thompson, S., Rutka, J., Michalski, J., Woo, S., Blaney, S. M., Kun, L. E., and Horowitz, A. M. (2006) A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group, J. Neurooncol. 77, 193-198

151. Lopez de Saro, F. J., Marinus, M. G., Modrich, P., and O'Donnell, M. (2006) The b Sliding Clamp Binds to Multiple Sites within MutL and MutS, J. Biol. Chem. 281, 14340-14349.

152. Kadyrov, F. A., Dzantiev, L., Constantin, N., and Modrich, P. (2006) Endonucleolytic function of MutLa in human mismatch repair, Cell 126, 297-308.

153. York, S. J. and Modrich, P. (2006) Mismatch repair-dependent iterative excision at irreparable O6- methylguanine lesions in human nuclear extracts, J. Biol. Chem. 281, 22674-22683, PMCID: PMC2234603.

154. Modrich, P. (2006) Mechanisms in eukaryotic mismatch repair, J. Biol. Chem. 281, 30305-30309, PMCID: PMC2234602.

155. Warren, J. J., Pohlhaus, T. J., Changela, A., Iyer, R. R., Modrich, P. L., and Beese, L. S. (2007) Structure of the human MutSa DNA lesion recognition complex, Mol. Cell 26, 579-592.

156 Pluciennik, A. and Modrich, P. (2007) Protein roadblocks and helix discontinuities are barriers to the initiation of mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 104, 12709-12713, PMCID: PMC1913546.

157. Sacho, E. J., Kadyrov, K. A., Modrich, P., Kunkel, T. A. and Erie, D. A. (2007) Direct Visualization of asymmetric adenine nucleotide-induced conformational changes in MutLa, Mol. Cell 29, 112-121, PMCID: PMC2820111.

158. Kadyrov, F. A., Holmes, S. F., Arana, M. E., Lukianova, O. A., O’Donnell, M., Kunkel, T. A., and Modrich, P. (2007) Saccharomyces cerevisiae MutLa is a mismatch repair endonuclease, J. Biol. Chem. 282, 37181– 37190, PMCID: PMC2302834.

159. Iyer, R. R., Pohlhaus, T. J., Chen, S., Hura, G. L., Dzantiev, L., Beese, L. S. and Modrich, P. (2008) The MutSa- PCNA Interaction in Human DNA Mismatch Repair, J. Biol. Chem. 283, 13310-13319, PMCID: PMC2423938.

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160. Maxwell, J. A., Johnson, S. P., McLendon, R. E., Lister, D. W., Horne, K. S., Rasheed, A., Quinn, J. A., Ali- Osman, F., Friedman, A. H., Modrich, P. L., Bigner, D. D. and Friedman, H. S. (2008) Mismatch repair deficiency does not mediate clinical resistance to Temozolomide in malignant glioma, Clin. Cancer Res., 14, 4859-4868, PMCID: PMC2830553.

161. Nimonkar, A. V., Özsoy, A. Z., Genschel, J., Modrich, P. and Kowalczykowski, S. C. (2008) Human exonuclease 1 and BLM helicase interact to initiate recombinational DNA repair, Proc. Natl. Acad. Sci. U. S. A. 105, 16906-16911, PMCID:PMC2579351.

162. Kadyrov, F. A., Genschel, J., Fang, Y., Penland, E., Edelmann, W, and Modrich, P. (2009) A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 106, 8495-8500, PMCID: PMC2677980.

163. Zhao, J., Jain, A., Iyer, R. R., Modrich, P. L., and Vasquez, K. M. (2009) Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks, Nucleic Acids Res. 37, 4420-4429, PMCID: PMCID: PMC2715249.

164. Genschel, J. and Modrich, P. (2009) Functions of MutLa, RPA, and HMGB1 in 5’-directed mismatch repair, J. Biol. Chem. 284, 21536-21544, PMCID: PMC2755878.

165. Pluciennik, A., Burdett, V., Lukianova, O., O'Donnell, M., and Modrich, P. (2009) Involvement of the beta clamp in methyl-directed mismatch repair in vitro, J. Biol. Chem. 284, 32782–32791, PMCID: PMC2781695.

166. Liu, Y., Fang, Y., Shao, H., Lindsey-Boltz, L., Sancar, A., and Modrich, P. (2010) Interactions of human mismatch repair proteins MutSa and MutLa with proteins of the ATR-Chk1 pathway, J. Biol. Chem. 285, 5974–5982, PMCID: PMC2820822.

167. Iyer, R. R., Pluciennik, A., Genschel, J., Tsai, M.-S., Beese, L. S., and Modrich, P. (2010) MutLa and PCNA share binding sites on MutSb, J. Biol. Chem. 285, 11730–11739, PMCID: PMC2857047.

168. Pillon, M. C., Lorenowicz, J. J., Uckelmann, M., Klocko, A. D., Mitchell, R. R., Chung, Y. S., Modrich, P., Walker, G. C., Simmons, L. A., Friedhoff, P., and Guarne, A. (2010) Structure of the endonuclease domain of MutL: Unlicensed to cut, Mol. Cell 39, 145-151, PMCID: PMC2933357.

169. van Oers, J. M. M., Roa, S., Werling, U., Liu, Y., Genschel, J., Hou, H. Jr., Sellers, R. S., Modrich, P., Scharff, M. D. and Edelmann, W. (2010) PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance, Proc. Natl. Acad. Sci. U. S. A. 107, 13384-13389, PMCID: PMC2922181.

170. Pluciennik, A., Dzantiev, L., Iyer, R. R., Constantin, N., Kadyrov, F. A. and Modrich, P. (2010) PCNA function in the activation and strand-direction of MutLa endonuclease in mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 107, 16066-16071, PMCID: PMC2941292.

171. Nimonkar, A. V., Genschel, J., Kinoshita, E., Polaczek, P., Campbell, J. L., Wyman, C., Modrich, P. and Kowalczykowski, S. C. (2011) BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA-break repair, Genes Dev. 25, 350-362, PMCID: PMC3042158.

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172. Orans, J., McSweeney, E. A., Iyer, R. R., Hellinga, H. W., Modrich, P. and Beese, L. S. (2011) Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family, Cell 145, 212-223, PMCID: 3093132.

173. Tseng, Q., Orans, J., Hast, M. A., Iyer, R. R., Changela, A., Modrich, P. L., and Beese, L. S. (2011) Purification, crystallization, and preliminary X-ray diffraction analysis of human mismatch repair protein MutSβ, Acta Crystallogr. Sect F Struct. Biol. Cryst. Commun. 67 Pt 8, 947-952, PMCID: 3151135.

174. Liu, Y., Kadyrov, F. A., and Modrich, P. (2011) PARP-1 enhances the mismatch-dependence of 5’-directed excision in human mismatch repair in vitro, DNA Repair 10, 1145-1153, PMCID: 3222275.

175. Pluciennik, A., Burdett, V., Baitinger, C., Iyer, R. R., Shi, K. and Modrich, P. (2013) Extrahelical (CAG)/(CTG) triplet repeat elements support proliferating cell nuclear antigen loading and MutLa endonuclease activation, Proc. Natl. Acad. Sci. U. S. A. 110, 12277-12282, PMCID: PMC3725108.

176. Dowhan, W., Nikaido, H., Stubbe, J., Kozarich, J.W., Wickner, W.T., Russell, D.W., Garrett, T.A., Brozek, K., and Modrich, P. (2013) Christian Raetz: scientist and friend extraordinaire, Ann. Rev. Biochem. 82, 1-24.

177. Lindsey-Boltz, L.A., Kemp, M.G., Reardon, J.T., DeRocco, V, Iyer, R.R., Modrich, P., and Sancar, A. (2014) Coupling of Human DNA Excision Repair and the DNA Damage Checkpoint in a Defined in Vitro System, J. Biol. Chem. 289, 5074-5082, PMCID: PMC3931066.

178. Shao, H., Baitinger, C., Soderblom, E. J., Burdett, V., and Modrich, P. (2014) Hydrolytic function of Exo1 in mammalian mismatch repair, Nucleic Acids Res. 42, 7104-7112, PMCID: PMC4066806.

179. Qiu, R., Sakato, M., Sacho, E.J., Wilkins, H., Zhang, X., Modrich, P., Hingorani, M.N., Erie, D.A., and Weninger, K.R. (2015) MutL traps MutS at a DNA mismatch, Proc. Natl. Acad. Sci. U. S. A. 112, 10194- 10919, PMCID: PMC4568282.

180. Chen, Y-T., Wu, J., Modrich, P. and Hsieh, T-s. (2016) Carboxyl-terminal 20 amino acids of Drosophila topoisomerase 2 are required for binding to a BRCT domain-containing protein Mus101 and fidelity of DNA segregation, J. Biol. Chem. 291, 13216-13228, PMCID: PMC4933235.

181. Modrich, P. (2016) Nobel Lecture: Mechanisms in E. coli and human mismatch repair, The Nobel Prizes 2015, 99-121, (ed. K. Grandin) The Nobel Foundation, Science History Publications/USA.

182. Modrich, P. (2016) Mechanisms in E. coli and human mismatch repair (Nobel Lecture), Angew. Chem. Int. Ed. 55, 8490-8501, PMCID: PMC5193110.

183. Genschel, J., Kadyrova, L.Y., Iyer, R.R., Dahal, B.K. Kadyrov, F.A., and Modrich, P. (2017) Interaction of proliferating cell nuclear antigen (PCNA) with PMS2 is required for MutLα activation and function in mismatch repair, Proc. Natl. Acad. Sci. U. S. A. 114, 4930–4935, PMCID: PMC5441711

184. Sherrer, S. M., Penland, E., and Modrich, P. (2018) The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease, Proc. Natl. Acad. Sci. U. S. A. 115, 7314-7319, Proc. Natl. Acad. Sci. U. S. A. 115, 7314-7319, PMCID: PMC6048502.

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185. Kadyrova, L.Y., Gujar, V., Burdett, V., Modrich, P.L., and Kadyrov, F.A. (2020) Human MutLγ, the MLH1– MLH3 heterodimer, is an endonuclease that promotes DNA expansion, Proc. Natl. Acad. Sci. U. S. A. 117, 3535-3542. PMCID: PMC7035508

PATENTS

Modrich, P., Su, S.-S., Au, K. G., and Lahue, R. S. (1995) Methods for mapping genetic mutations, U. S. Patent Number 5,459,039

Modrich, P. L., Su, S.-S., Au, K. G., Lahue, R. S., Cooper, D. L., and Worth, L. (1996) Methods and kits for fractionating a population of DNA molecules based on the presence or absence of a base-pair mismatch utilizing mismatch repair systems, U. S. Patent Number 5,556,750

Modrich, P. L., Su, S.-S., Au, K. G., Lahue, R. S., Cooper, D. L., and Worth, L. (1997) Methods of analysis and manipulating of DNA utilizing mismatch repair systems, U. S. Patent Number 5,679,522

Modrich, P. L., Su, S.-S., Au, K. G., Lahue, R. S., Cooper, D. L., and Worth, L. (1997) Methods of analysis and manipulating of DNA utilizing mismatch repair systems, U. S. Patent Number 5,702,894

Modrich, P. L., Su, S.-S., Au, K. G., Lahue, R. S., Cooper, D. L., and Worth, L. (1999) Solutions containing mismatch repair system proteins MutL and MutS, U. S. Patent Number 5,861,482

Modrich, P. L., Su, S.-S., Au, K. G., Lahue, R. S., Cooper, D. L., and Worth, L. (1999) Methods of analysis and manipulating of DNA utilizing mismatch repair systems, U. S. Patent Number 5,858,754

Modrich, P. L. and Smith, J. E. (1999) Methods for use of mismatch repair systems for the detection and removal of mutant sequences that arise during enzymatic amplification, U. S. Patent Number 5,922,539

Modrich, P. L., Iyer, R. R., Pluciennik, A., and Tsai, M.-S. (2014) Methods and Compositions for Identifying Inhibitors of MutSα or MutSβ interaction with MutLα, Patent Number 8623600.