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John Murnane, PhD

Title(s)Professor Emeritus, Radiation Oncology
SchoolSchool of Medicine
Phone415-476-9083
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    Collapse Biography 
    Collapse Education and Training
    University of California, Los AngelePhD06/1980Mircobiology and Immunology
    California State University, NorthridgeBS06/1971Chemistry

    Collapse Overview 
    Collapse Overview
    I am a molecular biologist interested in the role of genomic instability in cancer. Genomic instability is an early step in cancer that promotes tumor cell progression and resistance to therapy. My studies focus on the relationship between DNA repair and telomere loss, and the role of telomere loss in the extensive chromosome instability in cancer cells. Based on our earlier work, I have now developed a high-throughput assay that can detect small molecule inhibitors that target DNA double-strand break repair, telomere loss and chromosome instability, with the goal of identifying new cancer therapies.

    My earlier work was the first to demonstrate the importance of cell cycle regulation in cell survival in response to DNA damage (Nature, 1980), the ability of immortal human cells to maintain telomeres through a telomerase-independent mechanism (EMBO J, 1994), the ability of mammalian cells to repair broken chromosomes through the addition of a new telomere (PNAS, 1999), and the role of telomere loss in chromosome instability in human cancer due to the sensitivity of telomeric regioins to DNA double-strand breaks (Murnane, Reviewed in Cancer Res, 2010).

    Collapse Research 
    Collapse Research Activities and Funding
    Chromosome instability resulting from double-strand breaks near telomeres
    NIH/NCI R01CA120205Jul 6, 2006 - May 31, 2016
    Role: Principal Investigator
    Mechanisms of formation of terminal deletions
    NIH/NIEHS R01ES008427Jan 1, 1997 - May 31, 2009
    Role: Principal Investigator
    TELOMERIC REPEATS AND THE RESPONSE TO IONIZING RADIATION
    NIH/NCI R01CA069044May 15, 1996 - Mar 31, 2005
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Featured Publications
    Collapse Websites

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Liu Q, Lopez K, Murnane J, Humphrey T, Barcellos-Hoff MH. Misrepair in Context: TGFß Regulation of DNA Repair. Front Oncol. 2019; 9:799. PMID: 31552165.
      View in: PubMed
    2. Liu Q, Ma L, Jones T, Palomero L, Pujana MA, Martinez-Ruiz H, Ha PK, Murnane J, Cuartas I, Seoane J, Baumann M, Linge A, Barcellos-Hoff MH. Subjugation of TGFß Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining. Clin Cancer Res. 2018 12 01; 24(23):6001-6014. PMID: 30087144.
      View in: PubMed
    3. Muraki K, Murnane JP. The DNA damage response at dysfunctional telomeres, and at interstitial and subtelomeric DNA double-strand breaks. Genes Genet Syst. 2018 Jan 20; 92(3):135-152. PMID: 29162774.
      View in: PubMed
    4. Alcaraz Silva B, Jones TJ, Murnane JP. Differences in the recruitment of DNA repair proteins at subtelomeric and interstitial I-SceI endonuclease-induced DNA double-strand breaks. DNA Repair (Amst). 2017 01; 49:1-8. PMID: 27842255.
      View in: PubMed
    5. Janson C, Nyhan K, Murnane JP. Replication Stress and Telomere Dysfunction Are Present in Cultured Human Embryonic Stem Cells. Cytogenet Genome Res. 2015; 146(4):251-60. PMID: 26517359.
      View in: PubMed
    6. Muraki K, Han L, Miller D, Murnane JP. Processing by MRE11 is involved in the sensitivity of subtelomeric regions to DNA double-strand breaks. Nucleic Acids Res. 2015 Sep 18; 43(16):7911-30. PMID: 26209132.
      View in: PubMed
    7. Murnane JP. In memoriam: Robert Blair Painter. Radiat Res. 2015 Mar; 183(3):e49-50. PMID: 25763932.
      View in: PubMed
    8. Bakhoum SF, Kabeche L, Wood MD, Laucius CD, Qu D, Laughney AM, Reynolds GE, Louie RJ, Phillips J, Chan DA, Zaki BI, Murnane JP, Petritsch C, Compton DA. Numerical chromosomal instability mediates susceptibility to radiation treatment. Nat Commun. 2015 Jan 21; 6:5990. PMID: 25606712.
      View in: PubMed
    9. Kannarunimit D, Descovich M, Garcia A, Chen J, Weinberg V, Mcguinness C, Pinnaduwage D, Murnane J, Gottschalk AR, Yom SS. Analysis of dose distribution and risk of pneumonitis in stereotactic body radiation therapy for centrally located lung tumors: a comparison of robotic radiosurgery, helical tomotherapy and volumetric modulated arc therapy. Technol Cancer Res Treat. 2015 Feb; 14(1):49-60. PMID: 24325136.
      View in: PubMed
    10. Li Z, Wang H, Wang Y, Murnane JP, Dynan WS. Effect of radiation quality on mutagenic joining of enzymatically-induced DNA double-strand breaks in previously irradiated human cells. Radiat Res. 2014 Nov; 182(5):573-9. PMID: 25329962.
      View in: PubMed
    11. Bakhoum SF, Kabeche L, Murnane JP, Zaki BI, Compton DA. DNA-damage response during mitosis induces whole-chromosome missegregation. Cancer Discov. 2014 Nov; 4(11):1281-9. PMID: 25107667.
      View in: PubMed
    12. Li Z, Hudson FZ, Wang H, Wang Y, Bian Z, Murnane JP, Dynan WS. Increased mutagenic joining of enzymatically-induced DNA double-strand breaks in high-charge and energy particle irradiated human cells. Radiat Res. 2013 Jul; 180(1):17-24. PMID: 23692479.
      View in: PubMed
    13. Muraki K, Han L, Miller D, Murnane JP. The role of ATM in the deficiency in nonhomologous end-joining near telomeres in a human cancer cell line. PLoS Genet. 2013 Mar; 9(3):e1003386. PMID: 23555296.
      View in: PubMed
    14. Muraki K, Nyhan K, Han L, Murnane JP. Mechanisms of telomere loss and their consequences for chromosome instability. Front Oncol. 2012; 2:135. PMID: 23061048.
      View in: PubMed
    15. Reynolds GE, Gao Q, Miller D, Snow BE, Harrington LA, Murnane JP. PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells. DNA Repair (Amst). 2011 Nov 10; 10(11):1164-73. PMID: 21945094.
      View in: PubMed
    16. Murnane JP. Telomere dysfunction and chromosome instability. Mutat Res. 2012 Feb 01; 730(1-2):28-36. PMID: 21575645.
      View in: PubMed
    17. Miller D, Reynolds GE, Mejia R, Stark JM, Murnane JP. Subtelomeric regions in mammalian cells are deficient in DNA double-strand break repair. DNA Repair (Amst). 2011 May 05; 10(5):536-44. PMID: 21466975.
      View in: PubMed
    18. Murnane JP. Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res. 2010 Jun 01; 70(11):4255-9. PMID: 20484032.
      View in: PubMed
    19. Kulkarni A, Zschenker O, Reynolds G, Miller D, Murnane JP. Effect of telomere proximity on telomere position effect, chromosome healing, and sensitivity to DNA double-strand breaks in a human tumor cell line. Mol Cell Biol. 2010 Feb; 30(3):578-89. PMID: 19933847.
      View in: PubMed
    20. Zschenker O, Kulkarni A, Miller D, Reynolds GE, Granger-Locatelli M, Pottier G, Sabatier L, Murnane JP. Increased sensitivity of subtelomeric regions to DNA double-strand breaks in a human cancer cell line. DNA Repair (Amst). 2009 Aug 06; 8(8):886-900. PMID: 19540174.
      View in: PubMed
    21. Gao Q, Reynolds GE, Wilcox A, Miller D, Cheung P, Artandi SE, Murnane JP. Telomerase-dependent and -independent chromosome healing in mouse embryonic stem cells. DNA Repair (Amst). 2008 Aug 02; 7(8):1233-49. PMID: 18502190.
      View in: PubMed
    22. Ho CY, Murnane JP, Yeung AK, Ng HK, Lo AW. Telomeres acquire distinct heterochromatin characteristics during siRNA-induced RNA interference in mouse cells. Curr Biol. 2008 Feb 12; 18(3):183-7. PMID: 18261910.
      View in: PubMed
    23. Gao Q, Reynolds GE, Innes L, Pedram M, Jones E, Junabi M, Gao DW, Ricoul M, Sabatier L, Van Brocklin H, Franc BL, Murnane JP. Telomeric transgenes are silenced in adult mouse tissues and embryo fibroblasts but are expressed in embryonic stem cells. Stem Cells. 2007 Dec; 25(12):3085-92. PMID: 17823235.
      View in: PubMed
    24. Hosoi Y, Kapp LN, Murnane JP, Matsumoto Y, Enomoto A, Ono T, Miyagawa K. Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC. Biochem Biophys Res Commun. 2006 Sep 22; 348(2):728-34. PMID: 16890201.
      View in: PubMed
    25. Murnane JP. Telomeres and chromosome instability. DNA Repair (Amst). 2006 Sep 08; 5(9-10):1082-92. PMID: 16784900.
      View in: PubMed
    26. Bailey SM, Murnane JP. Telomeres, chromosome instability and cancer. Nucleic Acids Res. 2006; 34(8):2408-17. PMID: 16682448.
      View in: PubMed
    27. Pedram M, Sprung CN, Gao Q, Lo AW, Reynolds GE, Murnane JP. Telomere position effect and silencing of transgenes near telomeres in the mouse. Mol Cell Biol. 2006 Mar; 26(5):1865-78. PMID: 16479005.
      View in: PubMed
    28. Volik S, Raphael BJ, Huang G, Stratton MR, Bignel G, Murnane J, Brebner JH, Bajsarowicz K, Paris PL, Tao Q, Kowbel D, Lapuk A, Shagin DA, Shagina IA, Gray JW, Cheng JF, de Jong PJ, Pevzner P, Collins C. Decoding the fine-scale structure of a breast cancer genome and transcriptome. Genome Res. 2006 Mar; 16(3):394-404. PMID: 16461635.
      View in: PubMed
    29. Sabatier L, Ricoul M, Pottier G, Murnane JP. The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol Cancer Res. 2005 Mar; 3(3):139-50. PMID: 15798094.
      View in: PubMed
    30. Murnane JP, Sabatier L. Chromosome rearrangements resulting from telomere dysfunction and their role in cancer. Bioessays. 2004 Nov; 26(11):1164-74. PMID: 15499579.
      View in: PubMed
    31. Desmaze C, Pirzio LM, Blaise R, Mondello C, Giulotto E, Murnane JP, Sabatier L. Interstitial telomeric repeats are not preferentially involved in radiation-induced chromosome aberrations in human cells. Cytogenet Genome Res. 2004; 104(1-4):123-30. PMID: 15162025.
      View in: PubMed
    32. Weier HU, Chu LW, Murnane JP, Weier JF. Applications and technical challenges of fluorescence in situ hybridization in stem cell research. Blood Cells Mol Dis. 2004 Jan-Feb; 32(1):68-76. PMID: 14757416.
      View in: PubMed
    33. Pirzio LM, Freulet-Marrière MA, Bai Y, Fouladi B, Murnane JP, Sabatier L, Desmaze C. Human fibroblasts expressing hTERT show remarkable karyotype stability even after exposure to ionizing radiation. Cytogenet Genome Res. 2004; 104(1-4):87-94. PMID: 15162019.
      View in: PubMed
    34. Bai Y, Murnane JP. Telomere instability in a human tumor cell line expressing NBS1 with mutations at sites phosphorylated by ATM. Mol Cancer Res. 2003 Dec; 1(14):1058-69. PMID: 14707289.
      View in: PubMed
    35. Bai Y, Murnane JP. Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Hum Genet. 2003 Sep; 113(4):337-47. PMID: 12827497.
      View in: PubMed
    36. Morales JF, Snow ET, Murnane JP. Environmental factors affecting transcription of the human L1 retrotransposon. II. Stressors. Mutagenesis. 2003 Mar; 18(2):151-8. PMID: 12621071.
      View in: PubMed
    37. Lo AW, Sabatier L, Fouladi B, Pottier G, Ricoul M, Murnane JP. DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line. Neoplasia. 2002 Nov-Dec; 4(6):531-8. PMID: 12407447.
      View in: PubMed
    38. Lo AW, Sprung CN, Fouladi B, Pedram M, Sabatier L, Ricoul M, Reynolds GE, Murnane JP. Chromosome instability as a result of double-strand breaks near telomeres in mouse embryonic stem cells. Mol Cell Biol. 2002 Jul; 22(13):4836-50. PMID: 12052890.
      View in: PubMed
    39. Morales JF, Snow ET, Murnane JP. Environmental factors affecting transcription of the human L1 retrotransposon. I. Steroid hormone-like agents. Mutagenesis. 2002 May; 17(3):193-200. PMID: 11971989.
      View in: PubMed
    40. Schwartz JL, Jordan R, Liber H, Murnane JP, Evans HH. TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines. Genes Chromosomes Cancer. 2001 Mar; 30(3):236-44. PMID: 11170280.
      View in: PubMed
    41. Fouladi B, Sabatier L, Miller D, Pottier G, Murnane JP. The relationship between spontaneous telomere loss and chromosome instability in a human tumor cell line. Neoplasia. 2000 Nov-Dec; 2(6):540-54. PMID: 11228547.
      View in: PubMed
    42. Sprung CN, Afshar G, Chavez EA, Lansdorp P, Sabatier L, Murnane JP. Telomere instability in a human cancer cell line. Mutat Res. 1999 Oct 19; 429(2):209-23. PMID: 10526206.
      View in: PubMed
    43. Afshar G, Murnane JP. Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2. Gene. 1999 Jun 24; 234(1):161-8. PMID: 10393250.
      View in: PubMed
    44. Sprung CN, Reynolds GE, Jasin M, Murnane JP. Chromosome healing in mouse embryonic stem cells. Proc Natl Acad Sci U S A. 1999 Jun 08; 96(12):6781-6. PMID: 10359789.
      View in: PubMed
    45. Sprung CN, Sabatier L, Murnane JP. Telomere dynamics in a human cancer cell line. Exp Cell Res. 1999 Feb 25; 247(1):29-37. PMID: 10047445.
      View in: PubMed
    46. Schwartz JL, Murnane J, Weichselbaum RR. The contribution of DNA ploidy to radiation sensitivity in human tumour cell lines. Br J Cancer. 1999 Feb; 79(5-6):744-7. PMID: 10070863.
      View in: PubMed
    47. Desmaze C, Alberti C, Martins L, Pottier G, Sprung CN, Murnane JP, Sabatier L. The influence of interstitial telomeric sequences on chromosome instability in human cells. Cytogenet Cell Genet. 1999; 86(3-4):288-95. PMID: 10575228.
      View in: PubMed
    48. Sprung CN, Bryan TM, Reddel RR, Murnane JP. Normal telomere maintenance in immortal ataxia telangiectasia cell lines. Mutat Res. 1997 Oct 06; 379(2):177-84. PMID: 9357546.
      View in: PubMed
    49. Sprung CN, Sabatier L, Murnane JP. Effect of telomere length on telomeric gene expression. Nucleic Acids Res. 1996 Nov 01; 24(21):4336-40. PMID: 8932391.
      View in: PubMed
    50. Murnane JP. Role of induced genetic instability in the mutagenic effects of chemicals and radiation. Mutat Res. 1996 Jan; 367(1):11-23. PMID: 8596542.
      View in: PubMed
    51. Brzoska PM, Chen H, Zhu Y, Levin NA, Disatnik MH, Mochly-Rosen D, Murnane JP, Christman MF. The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. Proc Natl Acad Sci U S A. 1995 Aug 15; 92(17):7824-8. PMID: 7644499.
      View in: PubMed
    52. Murnane JP, Morales JF. Use of a mammalian interspersed repetitive (MIR) element in the coding and processing sequences of mammalian genes. Nucleic Acids Res. 1995 Aug 11; 23(15):2837-9. PMID: 7659505.
      View in: PubMed
    53. Hansell EJ, Frisch SM, Tremble P, Murnane JP, Werb Z. Simian virus 40 transformation alters the actin cytoskeleton, expression of matrix metalloproteinases and inhibitors of metalloproteinases, and invasive behavior of normal and ataxia-telangiectasia human skin fibroblasts. Biochem Cell Biol. 1995 Jul-Aug; 73(7-8):373-89. PMID: 8703410.
      View in: PubMed
    54. Morgan WF, Murnane JP. A role for genomic instability in cellular radioresistance? Cancer Metastasis Rev. 1995 Mar; 14(1):49-58. PMID: 7606821.
      View in: PubMed
    55. Murnane JP. Cell cycle regulation in response to DNA damage in mammalian cells: a historical perspective. Cancer Metastasis Rev. 1995 Mar; 14(1):17-29. PMID: 7606817.
      View in: PubMed
    56. Murnane JP, Zhu Y, Young BR, Christman MF. Expression of the candidate A-T gene ATDC is not detectable in a human cell line with a normal response to ionizing radiation. Int J Radiat Biol. 1994 Dec; 66(6 Suppl):S77-84. PMID: 7836856.
      View in: PubMed
    57. Murnane JP, Sabatier L, Marder BA, Morgan WF. Telomere dynamics in an immortal human cell line. EMBO J. 1994 Oct 17; 13(20):4953-62. PMID: 7957062.
      View in: PubMed
    58. van Loon N, Miller D, Murnane JP. Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination. Nucleic Acids Res. 1994 Jul 11; 22(13):2447-52. PMID: 8041604.
      View in: PubMed
    59. Leonhardt EA, Kapp LN, Young BR, Murnane JP. Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC). Genomics. 1994 Jan 01; 19(1):130-6. PMID: 8188213.
      View in: PubMed
    60. Murnane JP, Schwartz JL. Cell checkpoint and radiosensitivity. Nature. 1993 Sep 02; 365(6441):22. PMID: 8361532.
      View in: PubMed
    61. Richard CW, Cox DR, Kapp L, Murnane J, Cornelis F, Julier C, Lathrop GM, James MR. A radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia disease locus. Genomics. 1993 Jul; 17(1):1-5. PMID: 8406440.
      View in: PubMed
    62. Murnane JP, Kapp LN. A critical look at the association of human genetic syndromes with sensitivity to ionizing radiation. Semin Cancer Biol. 1993 Apr; 4(2):93-104. PMID: 8513152.
      View in: PubMed
    63. Murnane JP, Yu LC. Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break. Mol Cell Biol. 1993 Feb; 13(2):977-83. PMID: 8423817.
      View in: PubMed
    64. Kapp LN, Painter RB, Yu LC, van Loon N, Richard CW, James MR, Cox DR, Murnane JP. Cloning of a candidate gene for ataxia-telangiectasia group D. Am J Hum Genet. 1992 Jul; 51(1):45-54. PMID: 1609804.
      View in: PubMed
    65. Murnane JP. The role of recombinational hotspots in genome instability in mammalian cells. Bioessays. 1990 Dec; 12(12):577-81. PMID: 2080912.
      View in: PubMed
    66. Aggeler J, Murnane JP. Enhanced expression of procollagenase in ataxia-telangiectasia and xeroderma pigmentosum fibroblasts. In Vitro Cell Dev Biol. 1990 Sep; 26(9):915-22. PMID: 2172206.
      View in: PubMed
    67. Murnane JP, Yezzi MJ, Young BR. Recombination events during integration of transfected DNA into normal human cells. Nucleic Acids Res. 1990 May 11; 18(9):2733-8. PMID: 2339059.
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    68. Murnane JP. Influence of cellular sequences on instability of plasmid integration sites in human cells. Somat Cell Mol Genet. 1990 May; 16(3):195-209. PMID: 1972815.
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    69. Murnane JP, Young BR. Nucleotide sequence analysis of novel junctions near an unstable integrated plasmid in human cells. Gene. 1989 Dec 07; 84(1):201-5. PMID: 2606360.
      View in: PubMed
    70. Murnane JP, Yezzi MJ. Association of high rate of recombination with amplification of dominant selectable gene in human cells. Somat Cell Mol Genet. 1988 May; 14(3):273-86. PMID: 2835823.
      View in: PubMed
    71. Murnane JP. Inducible gene expression by DNA rearrangements in human cells. Mol Cell Biol. 1986 Feb; 6(2):549-58. PMID: 2431271.
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    72. Murnane JP, Fuller LF, Painter RB. Establishment and characterization of a permanent pSV ori--transformed ataxia-telangiectasia cell line. Exp Cell Res. 1985 May; 158(1):119-26. PMID: 2987007.
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    73. Murnane JP, Li GC. Effect of heat shock on the intracellular distribution of proteins. Radiat Res. 1985 Mar; 101(3):480-90. PMID: 4039070.
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    74. Morgan WF, Schwartz JL, Murnane JP, Wolff S. Effect of 3-aminobenzamide on sister chromatid exchange frequency in X-irradiated cells. Radiat Res. 1983 Mar; 93(3):567-71. PMID: 6856757.
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    75. Murnane JP, Painter RB. Altered protein synthesis in ataxia--telangiectasia fibroblasts. Biochemistry. 1983 Mar 01; 22(5):1217-22. PMID: 6838849.
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    76. Murnane JP, Painter RB. Complementation of the defects of DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells. Proc Natl Acad Sci U S A. 1982 Mar; 79(6):1960-3. PMID: 6952246.
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    77. Murnane JP, Byfield JE. Irreparable DNA cross-links and mammalian cell lethality with bifunctional alkylating agents. Chem Biol Interact. 1981 Dec; 38(1):75-86. PMID: 7326808.
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    78. Murnane JP, Byfield JE, Chen CT, Wang CH. The structure of methylated xanthines in relation to their effects on DNA synthesis and cell lethality in nitrogen mustard-treated cells. Biophys J. 1981 Sep; 35(3):665-76. PMID: 7272456.
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    79. Byfield JE, Murnane J, Ward JF, Calabro-Jones P, Lynch M, Kulhanian F. Mice, men, mustard and methylated xanthines: the potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents. Br J Cancer. 1981 May; 43(5):669-83. PMID: 7248151.
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    80. Murnane JP, Byfield JE, Ward JF, Calabro-Jones P. Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents. Nature. 1980 May 29; 285(5763):326-9. PMID: 7374784.
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    81. Fiala M, Heiner DC, Murnane J, Guze LB. Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen. J Med Virol. 1978; 2(1):39-44. PMID: 210253.
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    82. Fiala M, Honess RW, Heiner DC, Heine JW, Murnane J, Wallace R, Guze LB. Cytomegalovirus proteins. I. Polypeptides of virions and dense bodies. J Virol. 1976 Jul; 19(1):243-54. PMID: 181595.
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