ALAN S. WALDMAN

Alan S. Waldman

Professor of Biological Sciences
Ph.D., 1985, Johns Hopkins University
803-777-8405
awaldman@biol.sc.edu

Waldman Lab
Member: Center for Colon Cancer Research

Homologous Recombination in Mammalian Cells, Molecular Genetics, Gene Targeting, DNA Repair

Our laboratory group is interested in elucidating the mechanisms of homologous recombination (the exchange of genetic information between two similar DNA sequences) in mammalian cells. Homologous recombination plays important roles in gene expression, genetic diseases, DNA repair and the evolutionary process. Recombination can also be used as a tool in "gene targeting," a procedure in which a defined alteration is made to a chromosomal sequence through recombination with a DNA molecule introduced into a cell.? Our research encompasses both molecular genetic as well as biochemical approaches. A primary area that we have focused on is the issue of just how similar two chromosomal sequences must be in order to be recombined. We would like to understand why the homology requirement for recombination within mammalian chromosomes is normally very stringent and yet under certain circumstances (such as in cancer) sequences that are quite dissimilar are allowed to undergo rearrangements with one another. Another focus of our research involves the study of DNA repair, or more specifically, how cells repair breaks in chromosomes. We have engineered an experimental system which allows us to induce a single break in a chromosome in a living mammalian cell. We are using this system to learn how cells normally deal with such damage and how mutations associated with cancer may alter the cellular response to damage to the genome.

Selected Publications:

Yang, D., Goldsmith, E.B., Lin, Y., Waldman, B.C., Kaza, V., Waldman, A.S. (2006) Genetic Exchange Between Homeologous Sequences in Mammalian Chromosomes is Averted by Local Homology Requirements for Initiation and Resolution of Recombination, Genetics 174:135-144.

Smith, J.A., Waldman, B.C., and Waldman, A.S. (2005) A Role for Mismatch Repair Protein Msh2 in Error-Prone Double-Strand Break Repair in Mammalian Chromosomes, Genetics 170: 355-363.

Bannister, L.A., Waldman, B.C., and Waldman, A.S. (2004) Modulation of Error-Prone Double-Strand Break Repair in Mammalian Chromosomes by DNA Mismatch Repair Protein Mlh1, DNA Repair? 3: 465-474.

Smith, J.A., and Waldman, A.S. (2004) Determination of Intrachromosomal Recombination Rates in Cultured Mammalian Cells, pp 13- 23 in Genetic Recombination: Reviews and Protocols (A.S. Waldman, editor), Methods in Molecular Biology Series, vol. 262, Human Press, Totowa, NJ.

Waldman, A.S., editor (2004) Genetic Recombination: Reviews and Protocols, Methods in Molecular Biology Series, vol. 262, Human Press, Totowa, NJ.

Lin, Y., Waldman, B.C., and Waldman, A.S.(2003) Suppression of High-Fidelity Double-Strand Break Repair in Mammalian Chromosomes by Pifithrin- alpha, a Chemical Inhibitor of p53, DNA Repair 2: 1-11.

Lin, Y., and Waldman, A.S. (2001) Capture of DNA Sequences at Double-Strand Breaks in Mammalian Chromosomes. Genetics? 158:1665-1674.

Lin, Y., and Waldman, A.S.? (2001) Promiscuous Patching of Broken Chromosomes in Mammalian Cells with Extrachromosomal DNA. Nucleic Acids Res. 29: 3975-3981.

Lukacsovich, T., Waldman, B.C., and Waldman, A.S. (2001) Efficient Recruitment of Transfected DNA to a Homologous Chromosomal Target in Mammalian Cells. Biochim. Biophys. Acta 1521: 89-96.

Lukacsovich, T. and Waldman, A.S. (1999) Suppression of Intrachromosomal Gene Conversion in Mammalian Cells by Small Degrees of Sequence Divergence, Genetics 151:1559-1568.

Lin, Y., Lukacsovich, T., and Waldman, A.S. (1999) Multiple Pathways for Repair of DNA Double-strand Breaks in Mammalian Chromosomes, Mol. Cell. Biol. 19:8353-8360.

Waldman, A.S., Tran, H., Goldsmith, E.C., and Resnick, M.A. (1999) Long Inverted Repeats are an At-Risk Motif for Recombination in Mammalian Cells, Genetics 153:1873-1883.

Waldman, A.S. and Waldman, B.C. (1998) Stable Transfection of Mammalian Cells by Syringe-Mediated Mechanical Loading of DNA, Anal. Biochem. 258:216-222.

Yang, D. and Waldman, A.S. (1997) Fine Resolution Analysis of Products of Intrachromosomal Homeologous Recombination in Mammalian Cells, Mol. Cell. Biol. 17:3614-3628.

Waldman, B.C., O'Quinn, J. and Waldman, A.S. (1996) Enrichment for Gene Targeting in Mammalian Cells by Inhibition of Poly(ADP- ribosylation), Biochim. Biophys. Acta 1308:241- 250.

Esposito, D., Fitzmaurice, W.P., Benjamin, R.C., Goodman, S.D., Waldman, A.S., and Scocca, J.J. (1996) The Complete Nucleotide Sequence of Bacteriophage HP1 DNA, Nucleic Acids Res. 24:2360-2368.

Waldman, A.S. (1995) Molecular Mechanisms of Homologous Recombination, pp. 45-64 in Gene Targeting (edited by M. Vega), CRC Press, Boca Raton.

Waldman, A.S. (1994) The Search for Homology Does Not Limit the Rate of Extrachromosomal Homologous Recombination in Mammalian Cells, Genetics 136:597-605.

Yang, D. and Waldman, A.S. (1994) Production of Autoradiographs from Unfixed 35S-Labeled DNA Sequencing Gels, BioTechniques 16:224-226.

Lukacsovich, T., Yang, D. and Waldman, A.S. (1994) Repair of a Specific Double-Strand Break Generated Within a Mammalian Chromosome by Yeast Endonuclease I-SceI, Nucleic Acids Res. 22:5649-5657.

Yang, D. and Waldman, A.S. (1992) An Examination of the Effects of Double-Strand Breaks on Extrachromosomal Recombination in Mammalian Cells, Genetics 132:1080-1093.

Waldman, A.S. 1992. Targeted homologous recombination in mammalian cells, Critical. Rev. Oncology/Hematology 12:49-64.

Waldman, A.S. and Waldman, B.C. 1992. Stimulation of intrachromosomal homologous recombination in mammalian cells by an inhibitor of poly(ADP-ribosylation), Nucleic Acids Res. 21:5943-5947.

Waldman, B.C. and Waldman, A.S. 1990. Illegitimate and homologous recombination in mammalian cells: differential sensitivity to an inhibitor of poly(ADP-ribosylation), Nucleic Acids Res. 20:5981-5988.

Waldman, A.S. and Liskay, R.M. 1988. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology, Mol. Cell. Biol. 8:5350-5357.

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