David K. Orren, PhD | Toxicology and Cancer Biology

David K. Orren, PhD

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dkorre2@uky.edu
1095 V A Drive
356 HSRB

Position(s):

Associate Professor

Member of Markey Cancer Center

Affiliation(s):

Toxicology and Cancer Biology

Other Affiliation(s):

Toxicology - Joint Faculty

Interests / Specialties:

DNA damage and repair and their relationships to cancer and aging

Bio / Education:

B.A., 1979, Chemistry and Zoology, University of North Carolina at Chapel Hill
Ph.D., 1991, Biochemistry and Biophysics, University of North Carolina at Chapel Hill
Post-doctoral training, National Cancer Institute and National Institute on Aging, NIH

Research Description:

PubMed Publications:

Holcomb, N.;Goswami, M.;Han, S.G.;Scott, T.;D'Orazio, J.;Orren, D.K.;Gairola, C.G.;Mellon, I. "Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC." DNA repair 52, (2017): 70-80. [PubMed Link] | [ Full text ]
Orren, D.K. "The Nobel Prize in Chemistry 2015: Exciting discoveries in DNA repair by Aziz Sancar." Science China. Life sciences 59, 1 (2016): 97-102. [PubMed Link] | [ Full text ]
Holcomb, N.;Goswami, M.;Han, S.G.;Clark, S.;Orren, D.K.;Gairola, C.G.;Mellon, I. "Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway." PloS one 11, 7 (2016): e0158858. [PubMed Link] | [ Full text ]
Edwards, D.N.;Machwe, A.;Chen, L.;Bohr, V.A.;Orren, D.K. "The DNA structure and sequence preferences of WRN underlie its function in telomeric recombination events." Nature communications 6, (2015): 8331. [PubMed Link] | [ Full text ]
Edwards, D.N.;Orren, D.K.;Machwe, A. "Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2." Nucleic acids research 42, 12 (2014): 7748-61. [PubMed Link] | [ Full text ]
Lozada, E.;Yi, J.;Luo, J.;Orren, D.K. "Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities." Biogerontology 15, 4 (2014): 347-66. [PubMed Link] | [ Full text ]
Edwards, D.N.;Machwe, A.;Wang, Z.;Orren, D.K. "Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change." PloS one 9, 1 (2014): e80664. [PubMed Link] | [ Full text ]
Chan, N.L.;Hou, C.;Zhang, T.;Yuan, F.;Machwe, A.;Huang, J.;Orren, D.K.;Gu, L.;Li, G.M. "The Werner syndrome protein promotes CAG/CTG repeat stability by resolving large (CAG)(n)/(CTG)(n) hairpins." The Journal of biological chemistry 287, 36 (2012): 30151-6. [PubMed Link] | [ Full text ]
Machwe, A.;Lozada, E.;Wold, M.S.;Li, G.M.;Orren, D.K. "Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage." The Journal of biological chemistry 286, 5 (2011): 3497-508. [PubMed Link] | [ Full text ]
Machwe, A.;Karale, R.;Xu, X.;Liu, Y.;Orren, D.K. "The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks." Biochemistry 50, 32 (2011): 6774-88. [PubMed Link] | [ Full text ]
Li, K.;Wang, R.;Lozada, E.;Fan, W.;Orren, D.K.;Luo, J. "Acetylation of WRN protein regulates its stability by inhibiting ubiquitination." PloS one 5, 4 (2010): e10341. [PubMed Link] | [ Full text ]
Spencer, W.A.;Singh, J.;Orren, D.K. "Formation and differential repair of covalent DNA adducts generated by treatment of human cells with (+/-)-anti-dibenzo a,l pyrene-11,12-diol-13,14-epoxide." Chemical research in toxicology 22, 1 (2009): 81-9. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Lloyd, R.G.;Bolt, E.;Orren, D.K. "Replication fork regression in vitro by the Werner syndrome protein (WRN): holliday junction formation, the effect of leading arm structure and a potential role for WRN exonuclease activity." Nucleic acids research 35, 17 (2007): 5729-47. [PubMed Link] | [ Full text ]
Orren, D.K. "Werner syndrome: molecular insights into the relationships between defective DNA metabolism, genomic instability, cancer and aging." Frontiers in bioscience : a journal and virtual library 11, (2006): 2657-71. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Groden, J.;Orren, D.K. "The Werner and Bloom syndrome proteins catalyze regression of a model replication fork." Biochemistry 45, 47 (2006): 13939-46. [PubMed Link] | [ Full text ]
Machwe, A.;Lozada, E.M.;Xiao, L.;Orren, D.K. "Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins." BMC molecular biology 7, (2006): 1. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Orren, D.K. "Length-dependent degradation of single-stranded 3' ends by the Werner syndrome protein (WRN): implications for spatial orientation and coordinated 3' to 5' movement of its ATPase/helicase and exonuclease domains." BMC molecular biology 7, (2006): 6. [PubMed Link] | [ Full text ]
Orren, D.K. "The irresistible resistance of nonsense: Evolutionary adaptation of termination codons to minimize the effects of common DNA damage." DNA repair 4, 10 (2005): 1208-12. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Groden, J.;Matson, S.W.;Orren, D.K. "RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange." The Journal of biological chemistry 280, 24 (2005): 23397-407. [PubMed Link] | [ Full text ]
Lillard-Wetherell, K.;Machwe, A.;Langland, G.T.;Combs, K.A.;Behbehani, G.K.;Schonberg, S.A.;German, J.;Turchi, J.J.;Orren, D.K.;Groden, J. "Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2." Human molecular genetics 13, 17 (2004): 1919-32. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Orren, D.K. "TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA." Oncogene 23, 1 (2004): 149-56. [PubMed Link] | [ Full text ]
Orren, D.K.;Theodore, S.;Machwe, A. "The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro." Biochemistry 41, 46 (2002): 13483-8. [PubMed Link] | [ Full text ]
Machwe, A.;Xiao, L.;Theodore, S.;Orren, D.K. "DNase I footprinting and enhanced exonuclease function of the bipartite Werner syndrome protein (WRN) bound to partially melted duplex DNA." The Journal of biological chemistry 277, 6 (2002): 4492-504. [PubMed Link] | [ Full text ]
Orren, D.K.;Machwe, A.;Karmakar, P.;Piotrowski, J.;Cooper, M.P.;Bohr, V.A. "A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA." Nucleic acids research 29, 9 (2001): 1926-34. [PubMed Link] |
Machwe, A.;Orren, D.K.;Bohr, V.A. "Accelerated methylation of ribosomal RNA genes during the cellular senescence of Werner syndrome fibroblasts." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14, 12 (2000): 1715-24. [PubMed Link] | [ Full text ]
Machwe, A.;Ganunis, R.;Bohr, V.A.;Orren, D.K. "Selective blockage of the 3'-->5' exonuclease activity of WRN protein by certain oxidative modifications and bulky lesions in DNA." Nucleic acids research 28, 14 (2000): 2762-70. [PubMed Link] |
Ravn, P.;Kjaer, S.;Jensen, K.H.;Wind, T.;Jensen, K.B.;Kristensen, P.;Brosh, R.M.;Orren, D.K.;Bohr, V.A.;Clark, B.F. "Identification of phage antibodies toward the Werner protein by selection on Western blots." Electrophoresis 21, 3 (2000): 509-16. [PubMed Link] |
Cooper, M.P.;Machwe, A.;Orren, D.K.;Brosh, R.M.;Ramsden, D.;Bohr, V.A. "Ku complex interacts with and stimulates the Werner protein." Genes & development 14, 8 (2000): 907-12. [PubMed Link] | [ Full text ]
Orren, D.K.;Brosh RM, J.;Nehlin, J.O.;Machwe, A.;Gray, M.D.;Bohr, V.A. "Enzymatic and DNA binding properties of purified WRN protein: high affinity binding to single-stranded DNA but not to DNA damage induced by 4NQO." Nucleic acids research 27, 17 (1999): 3557-66. [PubMed Link] |
Brosh RM, J.;Orren, D.K.;Nehlin, J.O.;Ravn, P.H.;Kenny, M.K.;Machwe, A.;Bohr, V.A. "Functional and physical interaction between WRN helicase and human replication protein A." The Journal of biological chemistry 274, 26 (1999): 18341-50. [PubMed Link] | [ Full text ]
Balajee, A.S.;Machwe, A.;May, A.;Gray, M.D.;Oshima, J.;Martin, G.M.;Nehlin, J.O.;Brosh, R.;Orren, D.K.;Bohr, V.A. "The Werner syndrome protein is involved in RNA polymerase II transcription." Molecular biology of the cell 10, 8 (1999): 2655-68. [PubMed Link] | [ Full text ]
Bohr, V.A.;Dianov, G.;Balajee, A.;May, A.;Orren, D.K. "DNA repair and transcription in human premature aging disorders." The journal of investigative dermatology. Symposium proceedings 3, 1 (1998): 11-3. [PubMed Link] | [ Full text ]
Orren, D.K.;Petersen, L.N.;Bohr, V.A. "Persistent DNA damage inhibits S-phase and G2 progression, and results in apoptosis." Molecular biology of the cell 8, 6 (1997): 1129-42. [PubMed Link] | [ Full text ]
Kruk, P.A.;Orren, D.K.;Bohr, V.A. "Telomerase activity is elevated in early S phase in hamster cells." Biochemical and biophysical research communications 233, 3 (1997): 717-22. [PubMed Link] | [ Full text ]
Orren, D.K.;Dianov, G.L.;Bohr, V.A. "The human CSB (ERCC6) gene corrects the transcription-coupled repair defect in the CHO cell mutant UV61." Nucleic acids research 24, 17 (1996): 3317-22. [PubMed Link] |
Petersen, L.N.;Orren, D.K.;Bohr, V.A. "Gene-specific and strand-specific DNA repair in the G1 and G2 phases of the cell cycle." Molecular and cellular biology 15, 7 (1995): 3731-7. [PubMed Link] | [ Full text ]
Orren, D.K.;Petersen, L.N.;Bohr, V.A. "A UV-responsive G2 checkpoint in rodent cells." Molecular and cellular biology 15, 7 (1995): 3722-30. [PubMed Link] | [ Full text ]
Orren, D.K.;Selby, C.P.;Hearst, J.E.;Sancar, A. "Post-incision steps of nucleotide excision repair in Escherichia coli. Disassembly of the UvrBC-DNA complex by helicase II and DNA polymerase I." The Journal of biological chemistry 267, 2 (1992): 780-8. [PubMed Link] | [ Full text ]
Orren, D.K.;Sancar, A. "Formation and enzymatic properties of the UvrB.DNA complex." The Journal of biological chemistry 265, 26 (1990): 15796-803. [PubMed Link] | [ Full text ]
Orren, D.K.;Sancar, A. "The (A)BC excinuclease of Escherichia coli has only the UvrB and UvrC subunits in the incision complex." Proceedings of the National Academy of Sciences of the United States of America 86, 14 (1989): 5237-41. [PubMed Link] | [ Full text ]