Smerdon, Michael
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Research Interests
Our broad objective is to understand the molecular details of an important defense mechanism (DNA repair) against phenotypic changes in cells, and its modulation in different chromatin domains. Such changes are an important etiological factor in cell survival and cancer. DNA damage results from a wide variety of environmental agents, such as ultraviolet (UV) radiation and chemical carcinogens. Therefore, we use UV radiation and benzo[a]pyrene diol epoxide (BPDE) as prototype environmental agents for studies on nucleotide excision repair. In addition, repair of DNA strand breaks and methylated bases are used to elicit an alternative repair mode (base excision repair) which requires less processing at the chromatin level. We are examining the relationship between repair of these lesions and chromatin structure. The composition of nascent and mature repair sites in human and yeast chromatin is being analyzed. These studies employ novel analyses to follow repair at specific sites in different chromatin locations, including replication origins and transcribed genes. For example, we are currently examining DNA repair in a positioned nucleosome in cell-free extracts to answer well-defined questions about repair at the DNA-histone interface, and repair of different types of DNA lesions in RNA polymerase I and II genes in repair proficient and repair deficient yeast cells. Thus, we use a multifaceted approach to examine the role of chromatin structure and transcription in DNA damage and its repair in eukaryotes.

Publications (1998 - current)
Smerdon, M. J. and Thoma, F. Modulations in Chromatin Structure During DNA Damage Formation and DNA Repair. In: DNA Damage and Repair, Volume II: DNA Repair in Higher Eukaryotes, Nickoloff, J. A., and Hoekstra, M. F., eds., Humana Press Inc., Totowa, NJ, pp. 199-222, 1998.

Baxter, B. K. and Smerdon, M. J. Nucleosome Unfolding During DNA Repair in Normal and Xeroderma Pigmentosum (Group C) Human Cells. J. Biol. Chem. 273, 17517-17524, 1998.

Smerdon, M. J. and Conconi, A. Modulation of DNA Damage and DNA Repair in Chromatin. In: Progress in Nucleic Acids Research and Molecular Biology, Moldave, K., ed., Academic Press, Inc., vol. 62, pp 227-255, 1999.

Conconi, A., Liu, X., Koriazova, L., Ackerman, E. J. and Smerdon, M. J. Tight Correlation Between Inhibition of DNA Repair In Vitro and Transcription Factor IIIA Binding in the 5S Ribosomal Gene. EMBO J. 18, 1387-1396, 1999.

Li, S. and Smerdon, M. J. Base Excision Repair of N-methylpurines in a Yeast Minichromosome: Effects of Transcription, DNA Sequence and Nucleosome Positioning, J. Biol. Chem. 274, 12201-12204, 1999.

Meijer, M. and Smerdon, M. J. Accessing DNA Damage in Chromatin: Insights from Transcription, BioEssays 21, 596-603, 1999.

Kosmoski, J. V. and Smerdon, M. J. Synthesis and Nucleosome Structure of DNA containing a UV Photoproduct at a Specific Site, Biochemistry 38, 9485-9494, 1999.

Li, S., Livingstone-Zatchej, M., Gupta, R., Meijer, M., Thoma, F. and Smerdon, M. J. Nucleotide Excision Repair in a Constitutive and Inducible Gene of a Yeast Minichromosome in Intact Cells, Nucleic Acids Res. 27, 3610-3620, 1999.

Li, S., Waters, R. and Smerdon, M. J. Low and High Resolution Mapping of DNA Damage at Specific Sites, Methods: A Companion to Methods in Enzymology, vol. 22, pp. 170-179, 2000.

Conconi, A., Jager-Vottero, P., Zhang, X., Beard, B. C. and Smerdon, M. J. Mitotic Viability and Metabolic Competence in UV Irradiated Yeast Cells, Mutat.Res. 459, 55-64, 2000.

Liu, X., Mann, D. B., Suquet, C., Springer, D. L., and Smerdon, M. J. UV Damage and Nucleosome Folding of the 5S Ribosomal RNA Gene, Biochemistry 39, 557-566, 2000.

Brooks P. J., Wise, D. S., Berry, D. A., Kosmoski, J. V., Smerdon, M. J., Somers, R. L., Mackie, H., Spoonde, A. Y., Ackerman, E. J., Coleman, K., Tarone, R. E., and Robbins, J. H., The Oxidative DNA Lesion 8,5'-(S)-Cyclo-2'-deoxyadenosine is Repaired by the Nucleotide Excision Repair Pathway and Blocks Gene Expression in Mammalian Cells, J. Biol. Chem. 275, 22355-22362, 2000.

Liu, X. and Smerdon, M. J. Nucleotide Excision Repair of the 5S Ribosomal RNA Gene Assembled into a Nucleosome, J. Biol. Chem. 275, 23729-23735, 2000.

Bespalov, V. A., Conconi, A., X. Zhang, Fahy, D. and Smerdon, M. J. Improved Method for Measuring the Ensemble Average of Strand Breaks in Genomic DNA, Environ. Mol. Mutagen.-Special issue in honor of Dr. Richard B. Setlow, 38, 166-174, 2001.

Kosmoski, J. V., Ackerman, E. J. and Smerdon, M. J. DNA Repair of a Single UV Photo-product in a Designed Nucleosome, Proc. Natl. Acad. Sci. USA 98,10113-10118, 2001.

Conconi, A., Bespalov, V. A. and Smerdon, M. J. Transcription Coupled Repair in RNA Polymerase I Transcribed Genes of Yeast, Proc. Natl. Acad. Sci. USA 99, 649-654, 2002.

Li, S. and Smerdon, M. J. Yeast RNA polymerase II Subunits Mediate Subpathways of Transcription Coupled DNA Repair, EMBO J., submitted.

Li, S. and Smerdon, M. J. Nucleosome Structure and Repair of N-Methylpurines in the GAL1-10 Genes of Saccharomyces cerevisiae, J. Biol. Chem., submitted.