John Murnane, PhD
Professor Emeritus
Radiation Oncology
School of Medicine

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).

• High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.
  NAR cancer 2022 Wilson C, Murnane JP
• Telomeric Double Strand Breaks in G1 Human Cells Facilitate Formation of 5' C-Rich Overhangs and Recruitment of TERRA.
  Frontiers in genetics 2021 Nelson CB, Alturki TM, Luxton JJ, Taylor LE, Maranon DG, Muraki K, Murnane JP, Bailey SM
• Loss of TGFβ signaling increases alternative end-joining DNA repair that sensitizes to genotoxic therapies across cancer types.
  Science translational medicine 2021 Liu Q, Palomero L, Moore J, Guix I, Espín R, Aytés A, Mao JH, Paulovich AG, Whiteaker JR, Ivey RG, Iliakis G, Luo D, Chalmers AJ, Murnane J, Pujana MA, Barcellos-Hoff MH
• Defining the mutation signatures of DNA polymerase θ in cancer genomes.
  NAR cancer 2020 Hwang T, Reh S, Dunbayev Y, Zhong Y, Takata Y, Shen J, McBride KM, Murnane JP, Bhak J, Lee S, Wood RD, Takata KI
• Misrepair in Context: TGFβ Regulation of DNA Repair.
  Frontiers in oncology 2019 Liu Q, Lopez K, Murnane J, Humphrey T, Barcellos-Hoff MH
• Subjugation of TGFβ Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining.
  Clinical cancer research : an official journal of the American Association for Cancer Research 2018 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
• The DNA damage response at dysfunctional telomeres, and at interstitial and subtelomeric DNA double-strand breaks.
  Genes & genetic systems 2017 Muraki K, Murnane JP
• Differences in the recruitment of DNA repair proteins at subtelomeric and interstitial I-SceI endonuclease-induced DNA double-strand breaks.
  DNA repair 2016 Alcaraz Silva B, Jones TJ, Murnane JP
• Replication Stress and Telomere Dysfunction Are Present in Cultured Human Embryonic Stem Cells.
  Cytogenetic and genome research 2015 Janson C, Nyhan K, Murnane JP
• In memoriam: Robert Blair Painter.
  Radiation research 2015 Murnane JP
• Numerical chromosomal instability mediates susceptibility to radiation treatment.
  Nature communications 2015 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
• 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.
  Technology in cancer research & treatment 2014 Kannarunimit D, Descovich M, Garcia A, Chen J, Weinberg V, Mcguinness C, Pinnaduwage D, Murnane J, Gottschalk AR, Yom SS
• Effect of radiation quality on mutagenic joining of enzymatically-induced DNA double-strand breaks in previously irradiated human cells.
  Radiation research 2014 Li Z, Wang H, Wang Y, Murnane JP, Dynan WS
• DNA-damage response during mitosis induces whole-chromosome missegregation.
  Cancer discovery 2014 Bakhoum SF, Kabeche L, Murnane JP, Zaki BI, Compton DA
• Increased mutagenic joining of enzymatically-induced DNA double-strand breaks in high-charge and energy particle irradiated human cells.
  Radiation research 2013 Li Z, Hudson FZ, Wang H, Wang Y, Bian Z, Murnane JP, Dynan WS
• The role of ATM in the deficiency in nonhomologous end-joining near telomeres in a human cancer cell line.
  PLoS genetics 2013 Muraki K, Han L, Miller D, Murnane JP
• Mechanisms of telomere loss and their consequences for chromosome instability.
  Frontiers in oncology 2012 Muraki K, Nyhan K, Han L, 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 2011 Reynolds GE, Gao Q, Miller D, Snow BE, Harrington LA, Murnane JP
• Telomere dysfunction and chromosome instability.
  Mutation research 2011 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.
  Molecular and cellular biology 2009 Kulkarni A, Zschenker O, Reynolds G, Miller D, Murnane JP
• Increased sensitivity of subtelomeric regions to DNA double-strand breaks in a human cancer cell line.
  DNA repair 2009 Zschenker O, Kulkarni A, Miller D, Reynolds GE, Granger-Locatelli M, Pottier G, Sabatier L, Murnane JP
• Telomerase-dependent and -independent chromosome healing in mouse embryonic stem cells.
  DNA repair 2008 Gao Q, Reynolds GE, Wilcox A, Miller D, Cheung P, Artandi SE, Murnane JP
• Telomeres acquire distinct heterochromatin characteristics during siRNA-induced RNA interference in mouse cells.
  Current biology : CB 2008 Ho CY, Murnane JP, Yeung AK, Ng HK, Lo AW
• Telomeric transgenes are silenced in adult mouse tissues and embryo fibroblasts but are expressed in embryonic stem cells.
  Stem cells (Dayton, Ohio) 2007 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
• Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC.
  Biochemical and biophysical research communications 2006 Hosoi Y, Kapp LN, Murnane JP, Matsumoto Y, Enomoto A, Ono T, Miyagawa K
• Telomeres and chromosome instability.
  DNA repair 2006 Murnane JP
• Telomeres, chromosome instability and cancer.
  Nucleic acids research 2006 Bailey SM, Murnane JP
• Telomere position effect and silencing of transgenes near telomeres in the mouse.
  Molecular and cellular biology 2006 Pedram M, Sprung CN, Gao Q, Lo AW, Reynolds GE, Murnane JP
• Decoding the fine-scale structure of a breast cancer genome and transcriptome.
  Genome research 2006 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 …
• The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line.
  Molecular cancer research : MCR 2005 Sabatier L, Ricoul M, Pottier G, Murnane JP
• Chromosome rearrangements resulting from telomere dysfunction and their role in cancer.
  BioEssays : news and reviews in molecular, cellular and developmental biology 2004 Murnane JP, Sabatier L
• Applications and technical challenges of fluorescence in situ hybridization in stem cell research.
  Blood cells, molecules & diseases 2004 Weier HU, Chu LW, Murnane JP, Weier JF
• Human fibroblasts expressing hTERT show remarkable karyotype stability even after exposure to ionizing radiation.
  Cytogenetic and genome research 2004 Pirzio LM, Freulet-Marrière MA, Bai Y, Fouladi B, Murnane JP, Sabatier L, Desmaze C
• Interstitial telomeric repeats are not preferentially involved in radiation-induced chromosome aberrations in human cells.
  Cytogenetic and genome research 2004 Desmaze C, Pirzio LM, Blaise R, Mondello C, Giulotto E, Murnane JP, Sabatier L
• Telomere instability in a human tumor cell line expressing NBS1 with mutations at sites phosphorylated by ATM.
  Molecular cancer research : MCR 2003 Bai Y, Murnane JP
• Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein.
  Human genetics 2003 Bai Y, Murnane JP
• Environmental factors affecting transcription of the human L1 retrotransposon. II. Stressors.
  Mutagenesis 2003 Morales JF, Snow ET, Murnane JP
• DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line.
  Neoplasia (New York, N.Y.) 2002 Lo AW, Sabatier L, Fouladi B, Pottier G, Ricoul M, Murnane JP
• Chromosome instability as a result of double-strand breaks near telomeres in mouse embryonic stem cells.
  Molecular and cellular biology 2002 Lo AW, Sprung CN, Fouladi B, Pedram M, Sabatier L, Ricoul M, Reynolds GE, Murnane JP
• Environmental factors affecting transcription of the human L1 retrotransposon. I. Steroid hormone-like agents.
  Mutagenesis 2002 Morales JF, Snow ET, Murnane JP
• TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines.
  Genes, chromosomes & cancer 2001 Schwartz JL, Jordan R, Liber H, Murnane JP, Evans HH
• Telomere instability in a human cancer cell line.
  Mutation research 1999 Sprung CN, Afshar G, Chavez EA, Lansdorp P, Sabatier L, Murnane JP
• Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2.
  Gene 1999 Afshar G, Murnane JP
• Telomere dynamics in a human cancer cell line.
  Experimental cell research 1999 Sprung CN, Sabatier L, Murnane JP
• The contribution of DNA ploidy to radiation sensitivity in human tumour cell lines.
  British journal of cancer 1999 Schwartz JL, Murnane J, Weichselbaum RR
• The influence of interstitial telomeric sequences on chromosome instability in human cells.
  Cytogenetics and cell genetics 1999 Desmaze C, Alberti C, Martins L, Pottier G, Sprung CN, Murnane JP, Sabatier L
• Normal telomere maintenance in immortal ataxia telangiectasia cell lines.
  Mutation research 1997 Sprung CN, Bryan TM, Reddel RR, Murnane JP
• Effect of telomere length on telomeric gene expression.
  Nucleic acids research 1996 Sprung CN, Sabatier L, Murnane JP
• Role of induced genetic instability in the mutagenic effects of chemicals and radiation.
  Mutation research 1996 Murnane JP
• The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor.
  Proceedings of the National Academy of Sciences of the United States of America 1995 Brzoska PM, Chen H, Zhu Y, Levin NA, Disatnik MH, Mochly-Rosen D, Murnane JP, Christman MF
• Use of a mammalian interspersed repetitive (MIR) element in the coding and processing sequences of mammalian genes.
  Nucleic acids research 1995 Murnane JP, Morales JF
• 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.
  Biochemistry and cell biology = Biochimie et biologie cellulaire 1995 Hansell EJ, Frisch SM, Tremble P, Murnane JP, Werb Z
• A role for genomic instability in cellular radioresistance?
  Cancer metastasis reviews 1995 Morgan WF, Murnane JP
• Cell cycle regulation in response to DNA damage in mammalian cells: a historical perspective.
  Cancer metastasis reviews 1995 Murnane JP
• Expression of the candidate A-T gene ATDC is not detectable in a human cell line with a normal response to ionizing radiation.
  International journal of radiation biology 1994 Murnane JP, Zhu Y, Young BR, Christman MF
• Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination.
  Nucleic acids research 1994 van Loon N, Miller D, Murnane JP
• Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC).
  Genomics 1994 Leonhardt EA, Kapp LN, Young BR, Murnane JP
• Cell checkpoint and radiosensitivity.
  Nature 1993 Murnane JP, Schwartz JL
• A radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia disease locus.
  Genomics 1993 Richard CW, Cox DR, Kapp L, Murnane J, Cornelis F, Julier C, Lathrop GM, James MR
• A critical look at the association of human genetic syndromes with sensitivity to ionizing radiation.
  Seminars in cancer biology 1993 Murnane JP, Kapp LN
• Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break.
  Molecular and cellular biology 1993 Murnane JP, Yu LC
• Cloning of a candidate gene for ataxia-telangiectasia group D.
  American journal of human genetics 1992 Kapp LN, Painter RB, Yu LC, van Loon N, Richard CW, James MR, Cox DR, Murnane JP
• The role of recombinational hotspots in genome instability in mammalian cells.
  BioEssays : news and reviews in molecular, cellular and developmental biology 1990 Murnane JP
• Enhanced expression of procollagenase in ataxia-telangiectasia and xeroderma pigmentosum fibroblasts.
  In vitro cellular & developmental biology : journal of the Tissue Culture Association 1990 Aggeler J, Murnane JP
• Recombination events during integration of transfected DNA into normal human cells.
  Nucleic acids research 1990 Murnane JP, Yezzi MJ, Young BR
• Influence of cellular sequences on instability of plasmid integration sites in human cells.
  Somatic cell and molecular genetics 1990 Murnane JP
• Nucleotide sequence analysis of novel junctions near an unstable integrated plasmid in human cells.
  Gene 1989 Murnane JP, Young BR
• Association of high rate of recombination with amplification of dominant selectable gene in human cells.
  Somatic cell and molecular genetics 1988 Murnane JP, Yezzi MJ
• Inducible gene expression by DNA rearrangements in human cells.
  Molecular and cellular biology 1986 Murnane JP
• Establishment and characterization of a permanent pSV ori--transformed ataxia-telangiectasia cell line.
  Experimental cell research 1985 Murnane JP, Fuller LF, Painter RB
• Effect of heat shock on the intracellular distribution of proteins.
  Radiation research 1985 Murnane JP, Li GC
• Altered protein synthesis in ataxia--telangiectasia fibroblasts.
  Biochemistry 1983 Murnane JP, Painter RB
• Effect of 3-aminobenzamide on sister chromatid exchange frequency in X-irradiated cells.
  Radiation research 1983 Morgan WF, Schwartz JL, Murnane JP, Wolff S
• Complementation of the defects of DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells.
  Proceedings of the National Academy of Sciences of the United States of America 1982 Murnane JP, Painter RB
• Irreparable DNA cross-links and mammalian cell lethality with bifunctional alkylating agents.
  Chemico-biological interactions 1981 Murnane JP, Byfield JE
• The structure of methylated xanthines in relation to their effects on DNA synthesis and cell lethality in nitrogen mustard-treated cells.
  Biophysical journal 1981 Murnane JP, Byfield JE, Chen CT, Wang CH
• Mice, men, mustard and methylated xanthines: the potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents.
  British journal of cancer 1981 Byfield JE, Murnane J, Ward JF, Calabro-Jones P, Lynch M, Kulhanian F
• Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen.
  Journal of medical virology 1978 Fiala M, Heiner DC, Murnane J, Guze LB
• Cytomegalovirus proteins. I. Polypeptides of virions and dense bodies.
  Journal of virology 1976 Fiala M, Honess RW, Heiner DC, Heine JW, Murnane J, Wallace R, Guze LB