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WaiMun Huang, Ph.D.

last modified 2008-07-08 14:55 — by Whitney Evans

1993 - present, Adjunct Professor, Department of Pathology, Division of Cell Biology and Immunology. University of Utah.

1990 - present, Adjunct Professor, Department of Biology, University of Utah.

WaiMun Huang, Ph.D.

Wai Mun Huang

Contact Info

Email Address: waimun.huang ((at)) path.utah.edu

Office Phone Number: 801-581-8489

Location: 5200 Emma Eccles Jones Medical Research Building

Research Lab: Wai Mun Huang's Lab

Also Works in: Wai Mun Huang's Lab  

Division: Cell Biology & Immunology

Supporting Staff:   Mark Malcolm, M.S.  

 

Titles:

  • 2000, Chair, PRT Department of Oncological Sciences

About WaiMun Huang, Ph.D.

Chromosome ends are protected and the DNA is not freely exposed.   Bacterial chromosomes and plasmids are usually circular hence they are also without free ends.   In unusual cases, an alternative conformation in the form of linear chromosomes and linear plasmids with covalent closed hairpin ends has been identified.   In these linear structures, one strand of the DNA duplex turns around and continues on to become its own complementary sequence; hence the DNA ends are again not free.   The enzymes that are responsible for generating these closed hairpin ends to allow the stable maintenance of linear chromosomes and linear plasmids are called protelomerases.   Our laboratory is interested in the structure, function and mechanism of action of this new class of protelomerases.   Thus far, protelomerases have been found mainly in gamma proteobacteria, Borrelia spirochetes and in some eukarytic brown algae viruses.   In some linear plasmids, they turn out to be the non-integrated prophages of lamda-like phages.   Protelomerases share limited amino acid sequence homology with members of tyrosine-recombinase family which use tyrosine as the active site with coordination from other conserved residues to conduct two rounds of transesterification reactions of concerted breakage and rejoining to exchange DNA strands.   In so doing, tyrosine-recombinases catalyze the insertion or removal of DNA sequences via sequence specific target sites.   Protelomerases, like topoisomerase IB and tyrosine-recombinases, also use a concerted breakage and rejoining mechanism via an active site tyrosine, but they conduct an intra-molecular reaction in a sequence specific manner to turn each of the two halves of the target site around to form two closed hair-pins ends.   We have been examining a collection of these protelomerases in a comparative study to learn the general and specific mechanistic details that govern this new class of enzymes.   We used as models the systems of linear plasmid generating systems from the more complexed phage systems of Klebsiella phage K02 and coli phage N15 to the bacterial linear chromosome generating system of Agrobacterium tumefaciens and Borrelia using genetics and biochemical means.

Another topic of continuing interest in our laboratory is in the examination of the structure and function of type II topoisomerases, the ubiquitous enzymes that are found in all living cells.   They also use a concerted breakage and rejoining mechanism to effect topological changes in DNA making them participants in various DNA transactions and are essential for cellular functions such as recombinations, transcriptions, replications and DNA segregations.   Cells frequently harbor more than one type II topoisomerases and all are essential.   In bacteria, the two type II enzymes are the homologous DNA gyrases and the topoisomerase IV's each containing two subunits.   In general, they have distinct enzymologic properties and cellular roles and the subunits are not interchangeable.   Yet there are organisms harboring only one type II enzyme indicating the one enzyme can do all type II functions in those cases. How are these unique enzymes different from the canonical gyrase and topo IV?   In small phages or viruses, host enzymes usually fulfill the roles of the needed topoisomerase functions.   More recently, new phage and viral encoded type II topoisomerases have been discovered. We are investigating under what circumstances are these new topoisomerases needed, how are they distinct from the classic enzymes of gyrase and topo IV as well as that of T4 topoisomerases.   As more atomic structures of subunits and domains of type II topoisomerases are being discovered and solved, a detailed picture and the structural rationale of what defines a gyrase and topo IV are emerging.   The comparative studies including these new topoisomerases will provide new insight into new domain organizations and functions into the general rules that govern type II topoisomerases.   Furthermore, since type II topoisomerases are targets of anti-bacterial drugs, these new topoisomerases will be valuable in applying new rational drug designs for this class of targeted drugs.


Selected Publications

  • Huang, W. M. and Ts'o, P. O. (1966). J. Mol. Biol. 16:523-543. Physiochemical basis of the recognition process in nucleic acid interactions I. Interactions of polyuridylic acid and nucleosides.
  • Ts'o, P. O. and Huang, W. M. (1967). Biochemistry 7:2954-2962. Physiochemical basis of the recognition process in nucleic acid interactions II. Interactions of polyuridylic acid and polycytidylic acid with nucleoside mono- and triphosphates.
  • Pitha, P. M., Huang, W. M. and Ts'o, P. O. (1968). Proc. Natl. Acad. Sci. USA 61:229-332. Physiochemical basis of the recognition process in nucleic acid interactions IV. Costacking as the cause of mispairing and intercalation in nucleic acid interactions.
  • Okomoto, K., Mudd, J. A., Mangan, J., Huang, W. M., Subbaiah, T. V. and Marmur, J. (1968). J. Mol. Biol. 34:413-438. Properties of the defective phage of Bacillus subtilis.
  • Huang, W. M. and Marmur, J. (1970). J. Mol. Biol. 47:591-593. The 5'-ends of defective phages of Bacillus subtilis.
  • Huang, W. M. and Marmur, J. (1970). J. Virol. 5:237-246. Characterization of inducible phages in Bacillus licheniformis.
  • Huang, W. M. and Lehman, I. R. (1972). J. Biol. Chem. 247:3139-3146. On the exonuclease activity of phage T4 DNA polymerase.
  • Huang, W. M. and Lehman, I. R. (1972). J. Biol. Chem. 247:7663-7667. Direction of translation of T4 DNA polymerase gene in vivo.
  • O'Farrell, P. Z., Gold, L. M. and Huang, W. M. (1973). J. Biol. Chem. 248:5499-5501. Identification of prereplicative bacteriophage T4 proteins.
  • Huang, W. M. and Buchanan, J. M. (1974). Proc. Natl. Acad. Sci. USA 71:2226-2230. Synergistic interactions of T4 early proteins concerned with their binding to DNA.
  • Huang, W. M. (1975). Virology 66:508-521. Membrane associated proteins of T4 infected E. coli.
  • Thorner, J., Huang, W. M. and Lehman, I. R. (1975). Virology 68:338-348. Energy dependent activation of the temperature-sensitive DNA polymerase induced by bacteriophage T4 gene 43 mutants.
  • Stetler, G. L., King, G. J. and Huang, W. M. (1979). Proc. Natl. Acad. Sci. USA 76:3737-3741. T4 DNA-delay proteins, required for specific DNA replication form a complex which has ATP-dependent DNA topoisomerase activity.
  • Huang, W. M. (1979). J. Virology 32:917-924. Inhibition of initiation of T4 DNA replication by perturbation of E. coli host membrane composition.
  • Casjens, S. and Huang, W. M. (1982) J. Mol. Biol. 157:287-298. Initiation of sequence package of bacteriophage P22 DNA.
  • King, G. J. and Huang, W. M. (1982). Proc. Natl. Acad. Sci. USA 79:7248-7252. Identification of the origins of T4 DNA replication.
  • Huang, W. M. (1983). T4 DNA replication on cellophane discs in The Bacteriophage T4 Book. Edited by C. Mathews et al., ASM publications.
  • Kreuzer, K. N. and Huang, W. M. (1983) T4 DNA topoisomerase in The Bacteriophage T4 Book. Edited by C. Mathews et al., ASM publications.
  • Huang, W. M., Wei, L. and Casjens, S. (1985). J. Biol. Chem. 260:8973-8977. Relationship between bacteriophage T4 and T6 DNA topoisomerases.
  • Wyckoff, E., Sampson, L., Hayden, M., Parr, R., Huang, W. M. and Casjens, S. (1986). Gene 43:283-288. Plasmid vectors useful in the study of translation initiation signals.
  • Huang, W. M. (1986). NAR 14:7379-7390. The 52-protein subunit of T4 DNA topoisomerase is homologous to the gyrA-protein of gyrase.
  • Huang, W. M. (1986). NAR 147751-7765. Nucleotide sequence of a type II DNA topoisomerase gene. Bacteriophage T4 gene 39.
  • Casjens, S., Huang, W. M., Hayden, M. and Parr, R. (1987). J. Mol. Biol. 194 :411-422 Initiation of bacteriophage P22 DNA packaging series: Analysis of a mutant which alters the DNA target specificity of the package apparatus.
  • Huang, W. M., Ao, S., Casjens, S. , Orlandi, R., Zeikus, R., Weiss, R., Winge, D. and Fang, M. (1988). Science 239 1005-1012. A persistent untranslated sequence within bacteriophage T4 DNA topoisomerase gene 60.
  • Sampson, L., Hendrix, R., Huang, W.M. and Casjens, S. (1988).Translation initiation controls the relative rates of expression of the bacteriophage l late genes. Proc. Natl. Acad. Sci., USA 85 5439-5443.
  • Weiss, R., Huang, W. M. and Dunn, D. (1990) Cell 62 117-126. A nascent peptide is required for ribosomal bypass of the coding gap in bacteriophage T4 gene 60.
  • Casjen, S and Huang, W. M. (1993) Linear Chromosomal Physical and Genetic Map of Borrelia burgdorferi, the Lyme Disease Agent. Molec. Microbiology 8 967-980.
  • Wang, Y., Huang, W. M. and Taylor, D. (1993) Cloning and Nucleotide Sequence of Campylobacter jejuni gyrA Gene and Characterization of Quinolone Resistance Muatations. Antimicro Agents Chemother. 37, 457-463.
  • Takiff, H., Salazar, L., Guerrero, C., Philipp, W., Huang, W. M., Kreisworth, B., Cole, S., Jacobs, W. and Telenti, A. (1994) Cloning and nucleotide sequence of the Mycobacterium tuberculosis gyrA and gyrB genes, and characterization of quinolone resistance mutations. Antimicro. Agents Chemother. 38, 773-780.
  • Samuels, D. S., Marconi, R., Huang, W. M. and Garon, C. (1994) gyrB Mutations in coumermycin A1-resistant Borrelia burgdorferi. J. Bacteriol. 176, 3072-3075.
  • Korten, V., Huang, W. M. and Murray, B.E. (1994) gyrA muations associated with fluoroquinolone resistance in Enterococcus faecalis: Analysis by polymerse chain reaction and direct DNA sequencing. Antimicro. Agents Chemother. 38, 2091-2094.
  • Belland, R., Morrison, S., Ison, C. and Huang, W. M. (1994) High-level ciprofloxacin resistance involves changes in both gyrA and parC in Neisseria gonorrhoeae. Molec. Microbiol 14, 371-380.
  • Casjens, S., Delange, M., Ley, H., Rosa, P. and Huang, W. M. (1995) Linear chromosomes of Lyme disease agent spirochetes: Genetic diversity and conservation of gene order. J. Bacteriol., 177, 2769-2780.
  • Dew-Jager, K., Yu, W. and Huang, W.M. (1995) The recA gene of Borrelia burgdorferi. Gene 167, 137-140.
  • Bailey, C., Younkins, R. Huang, W. M. and Bott, K. (1996) Characterization of genes encoding topoisomerase IV of Mycoplasma genitialium. Gene, 168, 77-80.
  • Huang, W. M. (1996) Bacterial diversity based on typeII DNA topoisomerase genes. Annu. Rev. Genet. 30 79-107.
  • Casjens, S., Murphy, M., Delange, M., Sampson, L., can Vugt, R. and Huang, W. M. (1997) Telomeres of the linear chromosomes of Lyme disease spirochetes: nucleotide sequence and possible exchange with linear plasmid telomeres. Mol. Microbiol. 26, 581-596.
  • Fraser, C. M., Casjens, S., Huang, W. M. Clayton, R. White, O. et.al., (1997) Genome sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580-586.
  • Huang, W. M., Libbey, J., van der Hoeven, P.and Yu, S. (1998) Bipolar localization of Bacillus subtilis topoisomerase IV, a two subunit enzyme required for chromosome segregation. Proc. Natl. Acad. Sci., USA 95, 4652-4657.
  • Meier, P., Dooley, D., Jorgensen, J., Sanders, C. Huang, W. M. and Patterson, J. (1998) Development of quinolone-resistant Campylobacter fetus bacteremia in human immunodeficiency virus-infected patients. J. Infect. Dis. 177 951-954.
  • Kenny, G., Young, P., Cartwright, F., Sjostrom, K. and Huang, W. M. (1999) Sparfloxacin selects gyrase mutations in first-step Mycoplasma hominis mutants, whereas ofloxacin selects topoisomerase IV mutations. Antimicro. Agents Chemother. 43 2493-2496.
  • Casjens, S., Huang, W., Sutton, G., Peterson, J., Palmer, N., van Vugt, R., Stevenson, B., Rosa, P., Lathigra, R., and Fraser, C. (2000). A genome in transition: The twelve linear and nine circular extrachromosomal DNAs of an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi Molec. Micro.36, 490-516
  • Garcia-Lara, J., Picardeau, M., Hinnebusch, B., Huang, W. M. and Casjens, S. (2000) The role of genomics in approaching the study of Borrelia DNA replication. J. Mol. Microbiol. Biotechnol. 2 447-454.
  • Zuerner, R. and Huang, W. M. (2002) Analysis of a Leptospira interrogans locus containing DNA replication genes and a new IS, IS1502. FEMS Microbiology Letters 215 175-182.
  • Huang, W. M., Joss, L., Hsieh, T., and Casjens, S. (2004) Protelomerase uses a topoisomerase IB/Y-recombinase type mechanism to generate DNA hairpin ends. J. Mol. Biol. 337 77-92.
  • Casjens, S., Gilcrease, E., Huang, W. M., Bunny, K., Pedulla, F. M., Houtz, J., M., Hatfull, G. F., and Hendrix, R. (2004). The pKO2 linear plasmid prophage of Klebseilla oxytoca. J. Bacteriol. 186, 1818-1832.
  • Huang, W. M., Robertson, M., Aron, J. and Casjens, S. (2004) Telomere exchange between linear replicons of Borrelia burgdorferi. J. Bacteriol. 186 4143-4141.
  • Hsieh, T., Farh, L., Huang, W. M. and Chan, N. (2004) Structure of the Topoisomerase IV C-terminal Domain: A BROKEN {beta}-PROPELLER IMPLIES A ROLE AS GEOMETRY FACILITATOR IN CATALYSIS. J. Biol. Chem. 279, 55587-55593.
  • Duda, R., Hendrix, R., Huang, W. M. and Conway, J. (2006) Shared architecture of bacteriophage SP01 and herpesvirus capsids. Current Biology 16 R11-R13.
  • B. Books and book chapters
  • Huang, W. M. (1978). CSHSQB 43:495-499. Positive regulation of T even phage DNA replication by the DNA-delay protein of gene 39.
  • Huang, W. M. (1990) Virus encoded DNA topoisomerases. in "Biological Effects of DNA Topology". Edited by N. R. Cozzarelli and J. C. Wang, Cold Spring Harbor Laboratory.
  • Huang, W. M. (1990) Nucleotide sequences and the encoded amino acids of DNA topoisomerase genes. in "Biological Effects of DNA Topology". Edited by N. R. Cozzarelli and J. C. Wang, Cold Spring Harbor Laboratory.
  • Huang, W. M. (1992) Multiple DNA Gyrase-Like Genes in Eubacteria. in "DNA Topoisomerase in Chemotherapy" CRC Press.
  • Huang, W. M. (1994) Type II DNA Topoisomerase Genes. in "DNA Topoisomerases: Molecular Targets for Chemotherapy of Cancer and Infectious Diseases". Edited by L. F. Liu, Academic Press.
  • Huang, W. M. (1996) Bacterial diversity based on type II DNA topoisomerase genes. Annu. Rev. Genet. 30 79-107.
  • Casjens, S., and Huang, W. (1998). The linear chromosomes of B.burgdorferi and the other Lyme disease spirochetes. in Bacterial Genomes: Physical Structure and Analysis. Edited by F. de Bruijn, J. Lupski, and G. Weinstock. Chapman and Hall, New York, pp621-624.
  • Huang, W. M. (2001) PCR based cloning of DNA topoisomerase genes. In DNA topoisomerase protocols, Part II Enzymology and Drugs. Edited by Neil Osheroff and Mary-Ann Bjornsti Humana Press, Totowa, NJ, pp265-273.
  • García-Lara, J., Picardeau, M., Huang, W.M., Hinnebusch, J., and Casjens, S. (2001). The role of genomics in approaching the study of Borrelia DNA replication. In, The spirochetes: molecular and cellular biology, (Saier, M., and Garcia-Lara, G., Eds.) Horizon Scientific Press, Norfolk UK, pp127-136.
  • Huang, W., Ruan, Q. and Casjens, S. (2006) Hairpin telomeres of linear bacterial chromosomes and plasmids: How to make them. NATO Book on “Molecular Biology of Spirochetes” Edited by F. Cabello, IOS Press. Amsterdam.
  • Casjens, S. Huang, W., Gilcrease, E., Qiu, W., McCaig, W., Luft, B., Schutzer, S. and Fraser, C. (2006) Comparative genomics of Borrelia burgdorferi, NATO Book on “Molecular Biology of Spirochetes” Edited by F. Cabello, IOS Press, Amsterdam.
  • All Publications: Click Here

Professional Education

  • 1967, Ph.D. in Biophysical Chemistry, John Hopkins University, Md.
  • 1962, M.S. in Mathematics, Kansas State College, Kansas
  • 1961, B. Sc. Chinese University of Hon Kong