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Paula Traktman

TitleDean, College of Graduate Studies
InstitutionMedical University of South Carolina
DepartmentBiochemistry and Molecular Biology
AddressP.O. Box 501
BE101
Bioengineering Bldg - 68 President St.
Phone843-876-2405
Fax843-876-2416
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    Research Interests

    A: Vaccinia Virus: Vaccinia virus is the prototypic poxvirus and was the virus used in the vaccination campaign that led to the global eradication of smallpox. Vaccinia virus replicates solely within the cytoplasm of infected cells, and the 192 kb DNA genome encodes most, if not all, of the functions required for the progression of the viral life cycle. We have focused our attention primarily on viral DNA replication, the role of virally encoded kinases and phosphatases within the infectious cycle, and virion morphogenesis. We are also exploring the interplay between the viral life cycle and cellular bioenergetics. Our work integrates diverse approaches drawn from the disciplines of virology, molecular genetics, cell biology, and biochemistry.

    With regard to DNA replication, we are interested in understanding how replication is organized within dedicated cytoplasmic domains, in deciphering the mechanism of replication, and in pursuing a biochemical and genetic investigation of the proteins involved. We are interested in how the core polymerase, processivity factor (A20+UDG), single-strand DNA binding protein (I3), DNA ligase (A50), and FEN-1 like nuclease work together to accomplish faithful DNA replication and repair. Additionally, we are pursuing the hypothesis that the abundant H5 protein serves as a scaffold to support replication within the membrane-delimited cytoplasmic replication domains.

    figure 1

    With regard to virion morphogenesis, our current interest is focused on the biogenesis of the poxvirus membrane, which is quite unique and involves the enlargement of planar lipid bilayers within the cytoplasm. We are using a genetic, biochemical, cell biological and ultrastructural approaches to understand how the F10 kinase, a group of regulatory proteins (A6, A11, A30.5, H7, L2), and the two major structural proteins within the membrane (A14 and A17) mediate diversion of membranes from the endoplasmic reticulum (ER) and their remodeling and enlargement. The overall process of virion assembly involves a cascade of protein/protein, protein/DNA, and protein/lipid interactions that serve as an excellent model for the process of cellular organelle biogenesis.

    B: VRK1: A cellular protein kinase involved in nuclear architecture, mitotic and meiotic progression, cell proliferation, and oncogenesis.
    We became interested in the VRK family of cellular protein kinases because of the sequence similarity between their catalytic domains and that of the vaccinia-encoded B1 kinases. We performed the first thorough characterization of the VRK family (VRK1, nuclear; VRK2, nuclear envelope and ER; VRK3, nuclear pseudokinase) and purified and characterized their biochemical properties. We identified and validated the cellular BANF1 (BAF) protein as a highly efficient substrate for both VRK1. Within the interphase nucleus, BANF1 binds to chromatin and to proteins in the inner nuclear membrane (INM). We have shown that VRK1-mediated phosphorylation of BANF1, which peaks at the onset of mitosis, abrogates BANF’s DNA binding activity and reduces it’s interactions with proteins at the INM. VRK1 depletion leads to aberrant nuclear envelopes in interphase nuclei, and to the abnormal retention of BANF1 on chromosomes during early stages of mitosis (prophase, metaphase and anaphase). These effects have impacts on mitotic fidelity as well as cell proliferation.

    Because overexpression of VRK1 has shown to correlate with poor clinical outcome in a subset of breast cancer patients, we have focused much of our work on mammary epithelial cells (normal and malignant). Using a mouse xenograft model, we showed that malignant cells depleted of VRK1 formed smaller tumors than control cells, and that mice receiving this cells did not develop distal metastases. We have also shown that VRK1 overexpression accelerates acinus growth in a 3D culture model, but reduces cell migration in a 2D wound-healing model. We are using a variety of “omic” strategies, as well as cell biological and biochemical approaches, to understand the roles played by VRK1 in regulating cell structure and function in normal and cancerous cells.

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    Virology, Vaccinia, VRK1, oncogenesis, protein kinase

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Mon AM, MacKinnon AC, Traktman P. Overexpression of the VRK1 kinase, which is associated with breast cancer, induces a mesenchymal to epithelial transition in mammary epithelial cells. PLoS One. 2018; 13(9):e0203397. PMID: 30180179.
      View in: PubMed
    2. de Oliveira LC, Brasil BSAF, Unger B, Trindade GS, Abrahão JS, Kroon EG, Traktman P, Bonjardim CA. The Host Factor Early Growth Response Gene (EGR-1) Regulates Vaccinia virus Infectivity during Infection of Starved Mouse Cells. Viruses. 2018 03 21; 10(4). PMID: 29561772.
      View in: PubMed
    3. Meng X, Kaever T, Yan B, Traktman P, Zajonc DM, Peters B, Crotty S, Xiang Y. Characterization of murine antibody responses to vaccinia virus envelope protein A14 reveals an immunodominant antigen lacking of effective neutralization targets. Virology. 2018 05; 518:284-292. PMID: 29558682.
      View in: PubMed
    4. Greseth MD, Czarnecki MW, Bluma MS, Traktman P. Isolation and Characterization of v?I3 Confirm that Vaccinia Virus SSB Plays an Essential Role in Viral Replication. J Virol. 2018 01 15; 92(2). PMID: 29093092.
      View in: PubMed
    5. Cayo MA, Mallanna SK, Di Furio F, Jing R, Tolliver LB, Bures M, Urick A, Noto FK, Pashos EE, Greseth MD, Czarnecki M, Traktman P, Yang W, Morrisey EE, Grompe M, Rader DJ, Duncan SA. A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia. Cell Stem Cell. 2017 04 06; 20(4):478-489.e5. PMID: 28388428.
      View in: PubMed
    6. Greseth MD, Carter DC, Terhune SS, Traktman P. Proteomic Screen for Cellular Targets of the Vaccinia Virus F10 Protein Kinase Reveals that Phosphorylation of mDia Regulates Stress Fiber Formation. Mol Cell Proteomics. 2017 04; 16(4 suppl 1):S124-S143. PMID: 28183815.
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    7. Czarnecki MW, Traktman P. The vaccinia virus DNA polymerase and its processivity factor. Virus Res. 2017 04 15; 234:193-206. PMID: 28159613.
      View in: PubMed
    8. Oh HS, Traktman P, Knipe DM. Barrier-to-Autointegration Factor 1 (BAF/BANF1) Promotes Association of the SETD1A Histone Methyltransferase with Herpes Simplex Virus Immediate-Early Gene Promoters. MBio. 2015 May 26; 6(3):e00345-15. PMID: 26015494.
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    9. Boyle KA, Greseth MD, Traktman P. Genetic Confirmation that the H5 Protein Is Required for Vaccinia Virus DNA Replication. J Virol. 2015 Jun; 89(12):6312-27. PMID: 25855734.
      View in: PubMed
    10. Traktman P. Reflections of a Virologist and Unabashed Advocate for Basic Research. Annu Rev Virol. 2014 Nov 03; 1(1):vii-viii. PMID: 29084481.
      View in: PubMed
    11. Greseth MD, Traktman P. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection. PLoS Pathog. 2014 Mar; 10(3):e1004021. PMID: 24651651.
      View in: PubMed
    12. Molitor TP, Traktman P. Depletion of the protein kinase VRK1 disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes. Mol Biol Cell. 2014 Mar; 25(6):891-903. PMID: 24430874.
      View in: PubMed
    13. Molitor TP, Traktman P. Molecular genetic analysis of VRK1 in mammary epithelial cells: depletion slows proliferation in vitro and tumor growth and metastasis in vivo. Oncogenesis. 2013 Jun 03; 2:e48. PMID: 23732708.
      View in: PubMed
    14. Unger B, Mercer J, Boyle KA, Traktman P. Biogenesis of the vaccinia virus membrane: genetic and ultrastructural analysis of the contributions of the A14 and A17 proteins. J Virol. 2013 Jan; 87(2):1083-97. PMID: 23135725.
      View in: PubMed
    15. Greseth MD, Boyle KA, Bluma MS, Unger B, Wiebe MS, Soares-Martins JA, Wickramasekera NT, Wahlberg J, Traktman P. Molecular genetic and biochemical characterization of the vaccinia virus I3 protein, the replicative single-stranded DNA binding protein. J Virol. 2012 Jun; 86(11):6197-209. PMID: 22438556.
      View in: PubMed
    16. Pereira AC, Leite FG, Brasil BS, Soares-Martins JA, Torres AA, Pimenta PF, Souto-Padrón T, Traktman P, Ferreira PC, Kroon EG, Bonjardim CA. A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization. J Virol. 2012 Jan; 86(1):172-84. PMID: 22031940.
      View in: PubMed
    17. Boyle KA, Stanitsa ES, Greseth MD, Lindgren JK, Traktman P. Evaluation of the role of the vaccinia virus uracil DNA glycosylase and A20 proteins as intrinsic components of the DNA polymerase holoenzyme. J Biol Chem. 2011 Jul 15; 286(28):24702-13. PMID: 21572084.
      View in: PubMed
    18. Wickramasekera NT, Traktman P. Structure/Function analysis of the vaccinia virus F18 phosphoprotein, an abundant core component required for virion maturation and infectivity. J Virol. 2010 Jul; 84(13):6846-60. PMID: 20392848.
      View in: PubMed
    19. Wiebe MS, Nichols RJ, Molitor TP, Lindgren JK, Traktman P. Mice deficient in the serine/threonine protein kinase VRK1 are infertile due to a progressive loss of spermatogonia. Biol Reprod. 2010 Jan; 82(1):182-93. PMID: 19696012.
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    20. Unger B, Nichols RJ, Stanitsa ES, Traktman P. Functional characterization of the vaccinia virus I5 protein. Virol J. 2008 Dec 15; 5:148. PMID: 19077320.
      View in: PubMed
    21. Nichols RJ, Stanitsa E, Unger B, Traktman P. The vaccinia virus gene I2L encodes a membrane protein with an essential role in virion entry. J Virol. 2008 Oct; 82(20):10247-61. PMID: 18701587.
      View in: PubMed
    22. Wiebe MS, Traktman P. Poxviral B1 kinase overcomes barrier to autointegration factor, a host defense against virus replication. Cell Host Microbe. 2007 May 17; 1(3):187-97. PMID: 18005698.
      View in: PubMed
    23. Boyle KA, Arps L, Traktman P. Biochemical and genetic analysis of the vaccinia virus d5 protein: Multimerization-dependent ATPase activity is required to support viral DNA replication. J Virol. 2007 Jan; 81(2):844-59. PMID: 17093187.
      View in: PubMed
    24. Nichols RJ, Wiebe MS, Traktman P. The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. Mol Biol Cell. 2006 May; 17(5):2451-64. PMID: 16495336.
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    25. Condit RC, Moussatche N, Traktman P. In a nutshell: structure and assembly of the vaccinia virion. Adv Virus Res. 2006; 66:31-124. PMID: 16877059.
      View in: PubMed
    26. Stanitsa ES, Arps L, Traktman P. Vaccinia virus uracil DNA glycosylase interacts with the A20 protein to form a heterodimeric processivity factor for the viral DNA polymerase. J Biol Chem. 2006 Feb 10; 281(6):3439-51. PMID: 16326701.
      View in: PubMed
    27. Mercer J, Traktman P. Genetic and cell biological characterization of the vaccinia virus A30 and G7 phosphoproteins. J Virol. 2005 Jun; 79(11):7146-61. PMID: 15890954.
      View in: PubMed
    28. Punjabi A, Traktman P. Cell biological and functional characterization of the vaccinia virus F10 kinase: implications for the mechanism of virion morphogenesis. J Virol. 2005 Feb; 79(4):2171-90. PMID: 15681420.
      View in: PubMed
    29. Lefkowitz EJ, Upton C, Changayil SS, Buck C, Traktman P, Buller RM. Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource. Nucleic Acids Res. 2005 Jan 01; 33(Database issue):D311-6. PMID: 15608205.
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    30. Unger B, Traktman P. Vaccinia virus morphogenesis: a13 phosphoprotein is required for assembly of mature virions. J Virol. 2004 Aug; 78(16):8885-901. PMID: 15280497.
      View in: PubMed
    31. Boyle KA, Traktman P. Members of a novel family of mammalian protein kinases complement the DNA-negative phenotype of a vaccinia virus ts mutant defective in the B1 kinase. J Virol. 2004 Feb; 78(4):1992-2005. PMID: 14747564.
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    32. Traktman P, Boyle K. Methods for analysis of poxvirus DNA replication. Methods Mol Biol. 2004; 269:169-86. PMID: 15114016.
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    33. Nichols RJ, Traktman P. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J Biol Chem. 2004 Feb 27; 279(9):7934-46. PMID: 14645249.
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    34. Grubisha O, Traktman P. Genetic analysis of the vaccinia virus I6 telomere-binding protein uncovers a key role in genome encapsidation. J Virol. 2003 Oct; 77(20):10929-42. PMID: 14512543.
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    35. Mercer J, Traktman P. Investigation of structural and functional motifs within the vaccinia virus A14 phosphoprotein, an essential component of the virion membrane. J Virol. 2003 Aug; 77(16):8857-71. PMID: 12885904.
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    36. Lerch-Gaggl A, Haque J, Li J, Ning G, Traktman P, Duncan SA. Pescadillo is essential for nucleolar assembly, ribosome biogenesis, and mammalian cell proliferation. J Biol Chem. 2002 Nov 22; 277(47):45347-55. PMID: 12237316.
      View in: PubMed
    37. Punjabi A, Boyle K, DeMasi J, Grubisha O, Unger B, Khanna M, Traktman P. Clustered charge-to-alanine mutagenesis of the vaccinia virus A20 gene: temperature-sensitive mutants have a DNA-minus phenotype and are defective in the production of processive DNA polymerase activity. J Virol. 2001 Dec; 75(24):12308-18. PMID: 11711621.
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    38. Klemperer N, McDonald W, Boyle K, Unger B, Traktman P. The A20R protein is a stoichiometric component of the processive form of vaccinia virus DNA polymerase. J Virol. 2001 Dec; 75(24):12298-307. PMID: 11711620.
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    39. DeMasi J, Du S, Lennon D, Traktman P. Vaccinia virus telomeres: interaction with the viral I1, I6, and K4 proteins. J Virol. 2001 Nov; 75(21):10090-105. PMID: 11581377.
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    40. Najarro P, Traktman P, Lewis JA. Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation. J Virol. 2001 Apr; 75(7):3185-96. PMID: 11238845.
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    41. Traktman P, Liu K, DeMasi J, Rollins R, Jesty S, Unger B. Elucidating the essential role of the A14 phosphoprotein in vaccinia virus morphogenesis: construction and characterization of a tetracycline-inducible recombinant. J Virol. 2000 Apr; 74(8):3682-95. PMID: 10729144.
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    42. DeMasi J, Traktman P. Clustered charge-to-alanine mutagenesis of the vaccinia virus H5 gene: isolation of a dominant, temperature-sensitive mutant with a profound defect in morphogenesis. J Virol. 2000 Mar; 74(5):2393-405. PMID: 10666270.
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    43. Derrien M, Punjabi A, Khanna M, Grubisha O, Traktman P. Tyrosine phosphorylation of A17 during vaccinia virus infection: involvement of the H1 phosphatase and the F10 kinase. J Virol. 1999 Sep; 73(9):7287-96. PMID: 10438817.
      View in: PubMed
    44. Wilcock D, Duncan SA, Traktman P, Zhang WH, Smith GL. The vaccinia virus A4OR gene product is a nonstructural, type II membrane glycoprotein that is expressed at the cell surface. J Gen Virol. 1999 Aug; 80 ( Pt 8):2137-48. PMID: 10466813.
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    45. Rochester SC, Traktman P. Characterization of the single-stranded DNA binding protein encoded by the vaccinia virus I3 gene. J Virol. 1998 Apr; 72(4):2917-26. PMID: 9525612.
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    46. Klemperer N, Ward J, Evans E, Traktman P. The vaccinia virus I1 protein is essential for the assembly of mature virions. J Virol. 1997 Dec; 71(12):9285-94. PMID: 9371587.
      View in: PubMed
    47. McDonald WF, Klemperer N, Traktman P. Characterization of a processive form of the vaccinia virus DNA polymerase. Virology. 1997 Jul 21; 234(1):168-75. PMID: 9234958.
      View in: PubMed
    48. Song W, Kong HL, Traktman P, Crystal RG. Cytotoxic T lymphocyte responses to proteins encoded by heterologous transgenes transferred in vivo by adenoviral vectors. Hum Gene Ther. 1997 Jul 01; 8(10):1207-17. PMID: 9215738.
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    49. Du S, Traktman P. Vaccinia virus DNA replication: two hundred base pairs of telomeric sequence confer optimal replication efficiency on minichromosome templates. Proc Natl Acad Sci U S A. 1996 Sep 03; 93(18):9693-8. PMID: 8790393.
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    50. Liu K, Lemon B, Traktman P. The dual-specificity phosphatase encoded by vaccinia virus, VH1, is essential for viral transcription in vivo and in vitro. J Virol. 1995 Dec; 69(12):7823-34. PMID: 7494294.
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    51. Traktman P, Caligiuri A, Jesty SA, Liu K, Sankar U. Temperature-sensitive mutants with lesions in the vaccinia virus F10 kinase undergo arrest at the earliest stage of virion morphogenesis. J Virol. 1995 Oct; 69(10):6581-7. PMID: 7666563.
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    52. Evans E, Klemperer N, Ghosh R, Traktman P. The vaccinia virus D5 protein, which is required for DNA replication, is a nucleic acid-independent nucleoside triphosphatase. J Virol. 1995 Sep; 69(9):5353-61. PMID: 7636979.
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    53. Klemperer N, Lyttle DJ, Tauzin D, Traktman P, Robinson AJ. Identification and characterization of the orf virus type I topoisomerase. Virology. 1995 Jan 10; 206(1):203-15. PMID: 7831775.
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    54. McDonald WF, Traktman P. Vaccinia virus DNA polymerase. In vitro analysis of parameters affecting processivity. J Biol Chem. 1994 Dec 09; 269(49):31190-7. PMID: 7983061.
      View in: PubMed
    55. McDonald WF, Traktman P. Overexpression and purification of the vaccinia virus DNA polymerase. Protein Expr Purif. 1994 Aug; 5(4):409-21. PMID: 7950389.
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    56. Klemperer N, Traktman P. Biochemical analysis of mutant alleles of the vaccinia virus topoisomerase I carrying targeted substitutions in a highly conserved domain. J Biol Chem. 1993 Jul 25; 268(21):15887-99. PMID: 8393454.
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    57. Taddie JA, Traktman P. Genetic characterization of the vaccinia virus DNA polymerase: cytosine arabinoside resistance requires a variable lesion conferring phosphonoacetate resistance in conjunction with an invariant mutation localized to the 3'-5' exonuclease domain. J Virol. 1993 Jul; 67(7):4323-36. PMID: 8389930.
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    58. Rempel RE, Traktman P. Vaccinia virus B1 kinase: phenotypic analysis of temperature-sensitive mutants and enzymatic characterization of recombinant proteins. J Virol. 1992 Jul; 66(7):4413-26. PMID: 1602551.
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    59. McDonald WF, Crozel-Goudot V, Traktman P. Transient expression of the vaccinia virus DNA polymerase is an intrinsic feature of the early phase of infection and is unlinked to DNA replication and late gene expression. J Virol. 1992 Jan; 66(1):534-47. PMID: 1727498.
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    60. Evans E, Traktman P. Characterization of vaccinia virus DNA replication mutants with lesions in the D5 gene. Chromosoma. 1992; 102(1 Suppl):S72-82. PMID: 1291243.
      View in: PubMed
    61. Taddie JA, Traktman P. Genetic characterization of the vaccinia virus DNA polymerase: identification of point mutations conferring altered drug sensitivities and reduced fidelity. J Virol. 1991 Feb; 65(2):869-79. PMID: 1898973.
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    62. Tusie-Luna MT, Traktman P, White PC. Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus. J Biol Chem. 1990 Dec 05; 265(34):20916-22. PMID: 2249999.
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    63. Traktman P. Poxviruses: an emerging portrait of biological strategy. Cell. 1990 Aug 24; 62(4):621-6. PMID: 1974828.
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    64. Upton C, Opgenorth A, Traktman P, McFadden G. Identification and DNA sequence of the Shope fibroma virus DNA topoisomerase gene. Virology. 1990 Jun; 176(2):439-47. PMID: 2161144.
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    65. Nocka K, Tan JC, Chiu E, Chu TY, Ray P, Traktman P, Besmer P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J. 1990 Jun; 9(6):1805-13. PMID: 1693331.
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    66. Rempel RE, Anderson MK, Evans E, Traktman P. Temperature-sensitive vaccinia virus mutants identify a gene with an essential role in viral replication. J Virol. 1990 Feb; 64(2):574-83. PMID: 2296077.
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    67. Tan JC, Nocka K, Ray P, Traktman P, Besmer P. The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science. 1990 Jan 12; 247(4939):209-12. PMID: 1688471.
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    68. Traktman P. The enzymology of poxvirus DNA replication. Curr Top Microbiol Immunol. 1990; 163:93-123. PMID: 2242683.
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    69. Traktman P, Anderson MK, Rempel RE. Vaccinia virus encodes an essential gene with strong homology to protein kinases. J Biol Chem. 1989 Dec 25; 264(36):21458-61. PMID: 2600076.
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    70. Künzi MS, Traktman P. Genetic evidence for involvement of vaccinia virus DNA-dependent ATPase I in intermediate and late gene expression. J Virol. 1989 Sep; 63(9):3999-4010. PMID: 2527312.
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    71. Traktman P, Kelvin M, Pacheco S. Molecular genetic analysis of vaccinia virus DNA polymerase mutants. J Virol. 1989 Feb; 63(2):841-6. PMID: 2911123.
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    72. Oron Y, Straub RE, Traktman P, Gershengorn MC. Decreased TRH receptor mRNA activity precedes homologous downregulation: assay in oocytes. Science. 1987 Dec 04; 238(4832):1406-8. PMID: 2825350.
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    73. Evans E, Traktman P. Molecular genetic analysis of a vaccinia virus gene with an essential role in DNA replication. J Virol. 1987 Oct; 61(10):3152-62. PMID: 3041037.
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    74. Shaffer R, Traktman P. Vaccinia virus encapsidates a novel topoisomerase with the properties of a eucaryotic type I enzyme. J Biol Chem. 1987 Jul 05; 262(19):9309-15. PMID: 3036853.
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    75. Traktman P, Sridhar P, Condit RC, Roberts BE. Transcriptional mapping of the DNA polymerase gene of vaccinia virus. J Virol. 1984 Jan; 49(1):125-31. PMID: 6317886.
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    76. Traktman P, Baltimore D. Protease bypass of temperature-sensitive murine leukemia virus maturation mutants. J Virol. 1982 Dec; 44(3):1039-46. PMID: 6184485.
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    77. Goff S, Traktman P, Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981 Apr; 38(1):239-48. PMID: 6165830.
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    78. Hopkins N, Traktman P, Whalen K. N-Tropic variants obtained after co-infection with N- and B-tropic murine leukemia viruses. J Virol. 1976 Apr; 18(1):324-31. PMID: 176467.
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