John P. Murnane, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
John P. Murnane, PhD

Professor, Department of Radiation Oncology, UCSF
Wun-Kon Fu Endowed Chair in Radiation Oncology, UCSF

jmurnane@radonc.ucsf.edu

Phone: (415) 476-9083 (voice)
Box 0806, UCSF
San Francisco, CA 94143-0806

UCSF Profiles

Cancer Center Membership

Program Member ยป Cancer Genetics

Research Summary

My interests for many years have been mechanisms of DNA damage, DNA repair, and chromosome instability, and their relationship to cancer. My early work was the first to demonstrate that cell cycle regulation is important in protecting cells against DNA damage (Nature 285:326, 1980). My work was also the first to demonstrate that human cells can become immortal by maintaining telomeres through a process other than telomerase, and to propose that this mechanism involves recombination (EMBO J 13:4953, 1994). My laboratory was the first to establish a model system to demonstrate and monitor the ability of mammalian cells to stabilize broken chromosomes through the addition of new telomeres, called chromosome healing (PNAS 96:6781, 1999). My recent studies are focused on the role of telomere loss in the chromosome instability leading to human cancer cell progression and resistance to anti-cancer therapy. Our studies address the mechanism of sensitivity of subtelomeric regions to DNA double-strand breaks, and I have proposed that this sensitivity of telomeric regions to double-strand breaks is an important factor in chromosome instability in cancer (Cancer Res 70:4255, 2010). My laboratory is now involved in an in-depth analysis of the mechanisms responsible for this sensitivity of telomeric regions to double strand breaks and how to exploit this sensitivity and the ability of human cells to perform chromosome healing to limit the chromosome instability leading to tumor progression and resistance to cancer therapy.

Education

California State University, Northridge, B.S., 1971, Chemistry
University of California, Los Angeles, Ph.D., 1980, Microbiology and Immunology


Professional Experience

  • 1980-1983
    Postdoctoral Fellow, Laboratory of Radiobiology & Environmental Health, University of California, San Francisco
  • 1983-1984
    Asst. Research Biochemist, Laboratory of Radiobiology & Environmental Health, University of California, San Francisco
  • 1991-1995
    Associate Professor, Laboratory of Radiobiology & Environmental Health, University of California, San Francisco
  • 1995-1998
    Associate Professor, Department of Radiation Oncology, University of California, San Francisco
  • 2000-2004
    Assistant Professor, Laboratory of Radiobiology & Environmental Health, University of California, San Francisco
  • 1998-present
    Professor, Department of Radiation Oncology, University of California, San Francisco
  • 2007-present
    Vice Chairman, Department of Radiation Oncology, UCSF

Honors & Awards

  • 2007
    Margolis Lifetime Teaching Award, Department of Radiation Oncology, UCSF
  • 2009
    Wun-Kon Fu Endowed Chair in Radiation Oncology, Dept. of Radiation Oncology, UCSF

Selected Publications

  • Murnane, J.P., Byfield, J.E., Ward, J.F., and Calabro-Jones, P. Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents. Nature 285:326-329 (1980).
  • Murnane, J.P., Byfield, J.E., Chen, C.T., and Wang, C.H. The structure of methylated xanthines in relation to their effects on DNA synthesis and cell lethality in nitrogen mustard-treated cells. Biophys. J. 35:665-676 (1981).
  • Murnane, J.P., and Byfield, J.E. Irreparable DNA cross-links and mammalian cell lethality with bifunctional alkylating agents. Chemico-Biol. Interact. 38:75-86 (1981).
  • Byfield, J.E., Murnane, J.P., Ward, J.F., Calabro-Jones, P., Lynch, M., and Kulhanian, F. Mice, men, mustards and methylated xanthines: The potential role of caffeine and related drugs in the sensitization of human tumors to alkylating agents. British J. Cancer 43:669-683 (1981).
  • Murnane, J.P., and Painter, R.B. Complementation of the defects in DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells. Proc. Natl. Acad. Sci. 79:1960-1963 (1982).
  • Murnane, J.P., and Painter, R.B. Altered protein synthesis in ataxia-telangiectasia fibroblasts. Biochemistry 22:1217-1222 (1983).
  • Murnane, J.P. and Fuller, L.F. Isolation and characterization of a pSVori--transformed ataxia-telangiectasia cell line. Exp. Cell Res. 158:119-126 (1985).
  • Murnane, J.P. Inducible gene expression by DNA rearrangements in human cells. Mol. Cell. Biol. 6:549-558 (1986).
  • Murnane, J.P. and Yezzi, M.J. Association of a high rate of recombination with amplification of a dominant selectable gene in human cells. Somat. Cell Mol. Gen. 14:273-286 (1988).
  • Murnane, J.P. and Young, B.R. Nucleotide sequence analysis of novel junctions near a recombinational hotspot in human cells. Gene 84:201-205 (1989).
  • Murnane, J.P. Influence of cellular sequences on instability of plasmid integration sites in human cells. Somat. Cell Mol. Gen. 16:195-209 (1990).
  • Murnane, J.P., Yezzi, M.J., and Young, B.R. Recombination events during integration of transfected DNA into normal human cells. Nucl. Acids Res. 18:2733-2738 (1990).
  • Aggeler, J. and Murnane, J.P. Enhanced expression of procollagenase in ataxia-telangiectasia and xeroderma pigmentosum fibroblasts. In Vitro Cell. Dev. Biol. 26:915-922 (1990).
  • Murnane, J.P. The role of recombinational hotspots in genome instability in mammalian cells. BioEssays, 12:577-581 (1990).
  • Kapp, L.N., Painter, R.B., Yu, L.-C., van Loon, N., Richard, C.W., III, James, M.R., Cox, D.R. and Murnane, J.P. Cloning of a candidate gene for ataxia-telangiectasia group D. Am. J. Hum. Genet. 51:45-54 (1992).
  • Murnane, J.P. and Kapp, L.N. A critical look at the association of human genetic syndromes with sensitivity to ionizing radiation. Seminars in Cancer Biol., 4:93-104 (1993).
  • Murnane, J.P. and Yu, L.-C. Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break. Mol. Cell Biol., 13:977-983 (1993).
  • Murnane, J.P. and Schwartz, J.L. Cell checkpoint and radiosensitivity. Nature, 365:22 (1993).
  • Leonhardt, E.A, Kapp, L.N., Young, B.R. and Murnane, J.P. Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC). Genomics, 19:130-136 (1994).
  • van Loon, N., Miller, D. and Murnane, J.P. Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination. Nucleic Acids Res., 22:2447-2452 (1994).
  • Murnane, J.P., Sabatier, L., Marder, B. and Morgan, W.F. Telomere dynamics in an immortal human cell line. EMBO J., 13:4953-4962 (1994).
  • Murnane, J.P. Cell cycle delay in response to DNA damage in mammalian cells: a historical perspective. Cancer and Metast. Rev., issue on Cell cycle control and Genomic Instability, T. Tlsty, ed., 14:17-29 (1995).
  • Morgan, W.F. and Murnane, J.P. A role for genomic instability in cellular radioresistance? Cancer and Metast. Rev., issue on Cell cycle control and Genomic Instability, T. Tlsty, ed., 14:49-58 (1995).
  • Murnane, J.P. and Morales, J.F. Use of a mammalian interspersed repetitive (MIR) element in the coding and processing sequences of mammalian genes. Nucleic Acids Res., 23:2837-2839 (1995).
  • Murnane, J.P. Role of induced genetic instability in the mutagenic effects of chemicals and radiation. Mutat. Res., 367:11-23 (1996).
  • Sprung, C. N., Sabatier, L. and Murnane, J. P. Effect of telomere length on telomeric gene expression. Nucleic Acids Res., 24:4336-4340 (1996).
  • Sprung, C. N., Bryan, T. M., Reddel, R. R. and Murnane, J. P. Normal telomere maintenance in immortal ataxia telangiectasia cell lines. Mutat. Res., 379:177-184 (1997).
  • Sprung, C.N., Sabatier, L. and Murnane, J.P. Telomere dynamics in a human cancer cell line. Exp. Cell Res., 247:29-37 (1999).
  • Sprung, C.N., Reynolds, G. and Murnane, J.P. Chromosome healing in mouse embronic stem cells. Proc. Natl. Acad. Sci. USA, 96:6781-6786 (1999).
  • Afshar, G. and Murnane, J.P. Characterization of a human gene with homology to Saccharomyces cerevisiae SIR2. Gene, 234:161-168 (1999).
  • Sprung, C.N., Sabatier, L. and Murnane, J.P. Telomere instability in a human cancer cell line. Mutat. Res., 429:209-223 (1999).
  • Desmaze, C., Albert, C., Martins, L., Pottier, G., Sprung, C. N., Murnane, J.P. and Sabatier, L. The influence of interstitial telomeric repeat sequences on chromosomal instability in human cells. Cytogenet. Cell Genet., 86:288-295 (1999).
  • Fouladi, B, Miller, D., Sabatier, L. and Murnane, J.P. The role of spontaneous telomere loss in chromosome instability in a human tumor cell line. Neoplasia 2:540-554 (2000).
  • Schwartz, J.L., Jordan, R., Liber, H., Murnane, J.P. and Evans, H.H. TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines. Genes Chrom. Cancer 30:236-244 (2001).
  • Morales, J. F., Snow, E. T. and Murnane, J. P. Environmental factors affecting transcription of the human L1 retrotransposon: I. Steroid hormone-like agents. Mutagenesis 17:193-200 (2002).
  • Lo, A. W. I., Sprung, C., Fouladi, B., Pedram, M., Sabatier, L., Ricoul, M., Reynolds, G. E. and Murnane, J. P. Chromosome instability as a result of double-strand breaks near telomeres in mouse embryonic stem cells. Mol. Cell. Biol. 22:4836-4850 (2002).
  • Lo, A. W. I., Sabatier, L., Fouladi, B., Pottier, G, Ricoul, M., and Murnane, J. P. DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line. Neoplasia 4:531-538 (2002).
  • Morales, J. F., Snow, E. T. and Murnane, J. P. Environmental factors affecting transcription of the human L1 retrotransposon: II. Stressors. Mutagenesis, 18:151-158 (2003).
  • Bai, Y. and Murnane, J. P. Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Human Genetics, 113:337-347 (2003).
  • Desmaze, C., Pirzio, L. M., Blaise, R., Mondello, C., Giulotto, E., Murnane, J. P. and Sabatier, L. Interstitial telomeric repeats are not preferentially involved in radiation-induced chromosome aberrations. Cytogenet. Genome Res. 104:123-130 (2004).
  • Bai, Y. and Murnane, J. P. Telomere instability in a human tumor cell line expressing a NBS1 with mutations at sites of phosphorylation by ATM. Mol. Can. Res. 1:1058-1069 (2003).
  • Pirzio, L. M., Freulet-Marriere, M.-A., Bai, Y., Fouladi, B. Murnane, J. P., Sabatier, L. and Desmaze, C. Human fibroblasts expressing hTERT show remarkable karyotype stability even after exposure to ionizing radiation. Cytogenet. Genome Res. 104:87-94 (2004).
  • Murnane, J. P. and Sabatier, L. Chromosome rearrangements resulting from telomere dysfunction and their role in cancer. BioEssays, 26:1164-1174 (2004).
  • Murnane, J. P. The role of telomeres in genomic instability. In: Apoptosis and Senescence in Cancer Chemotherapy and Radiotherapy, Beverly Teicher, ed., Humana Press, Totowa, New Jersey (2005).
  • Sabatier, L., Ricoul, M., Pottier, G., Mathieu, N. and Murnane, J. P. The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol. Cancer Res., 3:139-150.
  • Volik, S., Raphael, B.J., Huang, G., Murnane, J., Waldman, F., Costello, J., Pienta, K., Mills, G., Brebner, J. H., Bajsarowicz K., Paris, P., Tao, Q., Kowbel, D., Lapuk, A., Kuo, W.-L., Shagin, D. A., Shagina, I. A., Gray, J. W., Cheng, J.-F., de Jong, P., Pevzner, P., and Collins, C. Decoding the fine-scale architecture of a breast cancer genome and transcriptome: Implications for a tumor genome project. Genome Research, 16:349-404 (2006).
  • Pedram, M., Sprung, C. N., Gao, Q., Lo, A. W. I., Reynolds, G. E., and Murnane, J. P. Telomere position effect and silencing of transgenes near telomeres in mouse. Mol. Cell. Biol., 26:1865-1878 (2006).
  • Bailey, S. M. and Murnane, J. P. Telomeres, Chromosome instability and Cancer. Nucleic Acids Res., Nucleic Acids Res., 34: 2408-2417 (2006).
  • Murnane, J. P. Telomeres and chromosome instability. Special issue on mechanisms of chromosome rearrangements. DNA repair, 5:1083-1092 (2006).