faculty

Michael Smerdon

Michael Smerdon

Regents Professor

smerdon@vetmed.wsu.edu

Office
Room: 147
Phone: 509-335-6853

Lab
Room: BLS 140
Phone: 509-335-7457

Lab Website

Lab Fax: 509-335-9688

 

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 by different chromatin domains. Such changes are an important etiological factor in cell survival and cancer. DNA damage results from a wide variety of exogenous agents, such as ultraviolet (UV) radiation and chemical carcinogens, and endogenous agents, such as reactive oxygen species. Therefore, we use UV radiation and benzo[a]pyrene diol epoxide (BPDE) as prototype environmental agents for studies on nucleotide excision repair. In addition, formation of uracil or methylated bases is used to elicit base excision repair, which requires less processing at the chromatin level. We are examining the relationship between repair of these lesions and chromatin structure in yeast and mammalian cells.

Our studies employ novel analyses to follow repair at specific sites in different chromatin locations, including transcribed genes and replication origins. For example, we are currently examining DNA repair in positioned nucleosomes 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, employing disciplines as distinct as yeast genetics and molecular biophysics, to examine the role of chromatin structure and transcription in DNA damage and its repair in eukaryotes.

Publications on PubMed

Select Publications

  • Mao P, Meas R, Dorgan KM, Smerdon MJ (2014) UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation Proc Natl Acad Sci U S A. 111(35), 12811-6 PMID: 25136098 PMCID: PMC4156752
  • Duan MR, Smerdon MJ (2014) Histone H3K14 Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of Chromatin Remodeler RSC J Biol Chem. 289(12), 8353-63 PMID: 24515106 PMCID: PMC3961661
  • Czaja W, Mao P, Smerdon MJ (2014) Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae. DNA Repair (Amst). 16, 35-43 PMID: 24674626 PMCID: PMC4026264
  • Zavala AG, Morris RT, Wyrick JJ, Smerdon MJ (2014) High-resolution characterization of CPD hotspot formation in human fibroblasts. Nucleic Acid Res. 42(2), 893-905 PMID: 24137003 PMCID: PMC3902913
  • Ghosh-Roy S, Das D, Chowdhury D, Smerdon MJ, Chaudhuri RN (2013) Rad26, the Transcription-Coupled Repair Factor in Yeast, Is Required for Removal of Stalled RNA Polymerase-II following UV Irradiation PLoS One 8(8) PMID: 23991048 PMCID: PMC3749123
  • Rodriguez Y, Smerdon MJ (2013) The Structural Location of DNA Lesions in Nucleosome Core Particles Determines Accessibility by Base Excision Repair Enzymes J Biol Chem. 288(19), 13863-75 PMID: 23543741 PMCID: PMC3650422
  • Shim Y, Duan MR, Chen X, Smerdon MJ, Min JH (2012) Polycistronic co-expression and non-denaturing purification of histone octamers Anal Biochem. 427, 190-192
  • Mao P, Smerdon MJ (2010) Yeast Deubiquitinase Ubp3 Interacts with the 26S Proteasome and Facilitates Rad4 degradation J Biol Chem. 285(48), 37542-50 PMID: 20876584 PMCID: PMC2988359
  • Hinz AK, Wang Y, Smerdon MJ (2010) Base Excision Repair in a Glucocorticoid Response Element: Affects of Glucocorticoid Receptor Binding J Biol Chem. 285(37), 28683-90 PMID: 20628060 PMCID: PMC2937895
  • Czaja W, Bespalov VA, Hinz JM, Smerdon MJ (2010) Proficient repair in chromatin remodeling defective ino80 mutants of Saccharomyces cerevisiae highlights replication defects as the main contributor to DNA damage sensitivity DNA Repair (Amst). 9(9), 976-84 PMID: 20674516 PMCID: PMC2929300
  • Duan MR, Smerdon MJ (2010) UV Damage in DNA Promotes Nucleosome Unwrapping J Biol Chem. 285(34), 26295-303 PMID: 20562439 PMCID: PMC2924050
  • Hinz JM, Rodriguez Y, Smerdon MJ (2010) Rotational Dynamics of DNA on the Nucleosome Surface Markedly Impact Accessibility to a DNA Repair Enzyme Proc Natl Acad Sci U S A. 107(10), 4646-51 PMID: 20176960 PMCID: PMC2842065
  • Nag R, Kyriss M, Smerdon JW, Wyrick JJ, Smerdon MJ (2010) A cassette of N-terminal amino acids of histone H2B are required for efficient cell survival, DNA repair and Swi/Snf binding in UV irradiated yeast Nucleic Acids Res. 38(5), 1450-60 PMID: 20007597 PMCID: PMC2836547
  • Nag R, Smerdon MJ (2009) Altering the Chromatin Landscape for Nucleotide Excision Repair Mutat Res. 682(1), 13-20 PMID: 19167517
  • Chaudhuri S, Wyrick JJ, Smerdon MJ (2009) Methylated Lysine Residues of Histone H3 are Required for Efficient DNA Repair at a Silenced Chromatin Locus in Saccharomyces cerevisiae Nucleic Acids Res. 37(5), 1690-700 PMID: 19155276 PMCID: PMC2655692
  • Nag R, Gong F, Fahy D, Smerdon MJ (2008) A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast. Nucleic Acids Res. 36(11), 3857-66 PMID: 18508805 PMCID: PMC2441814
  • Gong F, Fahy D, Liu H, Wang W, Smerdon MJ (2008) Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage. Cell Cycle. 7(8), 1067-74 PMID: 18414052
  • Maloney SC, Adair JE, Smerdon MJ, Reeves R (2007) Gene-specific nucleotide excision repair is impaired in human cells expressing elevated levels of high mobility group A1 nonhistone proteins DNA Repair (Amst). 6(9), 1371-9 PMID: 17540622 PMCID: PMC1994692
  • Adair JE, Maloney SC, Dement GA, Wertzler KJ, Smerdon MJ, Reeves R (2007) High mobility group A1 (HMGA1) proteins inhibit expression of nucleotide excision repair factor Cancer Res. 67(13), 6044-52 PMID: 17616660
  • Different structural states in oligonucleosomes are required for early versus late steps of base excision repair. (2007) Different structural states in oligonucleosomes are required for early versus late steps of base excision repair. Nucleic Acids Res. 35(13), 4313-21 PMID: 17576692 PMCID: PMC1934998
  • Zhang L, Jones K, Smerdon MJ, Gong F (2009) Assays for chromatin remodeling during nucleotide excision repair in Saccharomyces cerevisiae. Methods. 48(1), 19-22 PMID: 19336254 PMCID: PMC2692424
  • Czaja W, Mao P, Smerdon MJ (2012) The emerging roles of ATP-dependent chromatin remodeling enzymes in nucleotide excision repair. Int J Mol Sci. 13(9), 11954-73 PMID: 23109894 PMCID: PMC3472786
  • Gong F, Fahy D, Smerdon MJ (2006) Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. Nat Struct Mol Biol. 13(10), 902-7 PMID: 17013386
  • Li S, Chen X, Ruggiero C, Ding B, Smerdon MJ (2006) Modulation of Rad26 and Rpb9 Mediated DNA Repair by Different Promoter Elements J Biol Chem 281(48), 36643-51 PMID: 17023424 PMCID: PMC1913475
  • Gong F, Fahy D, Smerdon MJ (2006) Combination of chemical cross-linking and pull-down assay to study transient protein-protein interactions Nature Protocols NETWORK