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Bethany A. Buck

Beth Buck-KoehntopBIOLOGICAL & PHYSICAL CHEMISTRY

Associate Professor
Adjunct Associate Professor of Biochemistry
Associate Member, Huntsman Cancer Institute Cancer Center

Director, Biological Chemistry PhD Program

B.Sc., University of Wisconsin – Stevens Point, 2000
Ph.D., University of Minnesota, 2005
American Cancer Society Postdoctoral Fellow, The Scripps Research Institute, 2007-2010

 

Phone: (801) 581-3186
Office: 1493 GH
Email: bethany.buck@utah.edu

Research Group
Biophysics at the U
Biological Chemistry Program

Activities & Awards

  • Sigma Chi Fraternity Outstanding Faculty Award, 2016
  • Extraordinary Faculty Achievement Recognition Award, 2016
  • Career Services Faculty Recognition Award, 2016
  • American Cancer Society Research Scholar Grant, 2014
  • American Cancer Society Postdoctoral Fellowship, 2007

Research Interests

The primary focus of our research is to utilize a multidisciplinary approach incorporating structural biology, biophysics, biochemistry, molecular biology and cellular biology to investigate mechanistic questions in the area of transcriptional regulation. We are particularly interested in applying these methodologies to discern structure-function relationships for specialized transcription factors that recognize epigenetically modified methyl-CpG DNA sequences.

In eukaryotes, DNA methylation in the context of CpG dinucleotides is an essential epigenetic modification required for genomic stability, regulation of chromatin structure and long-term transcriptional silencing of genes. It is becoming increasingly evident that nearly all cancers exhibit aberrant alterations in DNA methylation preceding tumorigenesis. DNA methylation leads to alterations in gene transcription through two primary mechanisms: abrogating the ability of transcription factors to localize to their consensus sites or recruitment of specialized transcription factors that selectively recognize mCpG targets. These designated methyl-CpG binding proteins (MBPs) then promote recruitment of enzyme complexes that remodel chromatin and alter transcription. Thus, MBPs represent the functional intermediaries between reading DNA methylation and translating these epigenetic signals into a down-stream transcriptional response. However, detailed mechanistic insight for how MBPs globally mediate this essential cellular process remains to be elucidated.

Active areas of research in our laboratory include: 1) Utilizing a parallel in vitro biophysical/structural and in cell genomic approach to delineate the molecular mechanisms by which these proteins recognize their cognate DNA targets and regulate transcription in the cancerous state; 2) structural characterization of these MBP:DNA interactions to ascertain modes of mCpG recognition for various MBPs; and 3) structural and biophysical characterizations of protein/protein interactions in conjunction with high-throughput sequencing/bioinformatics strategies to begin evaluating how interpretation of the methylation signal mechanistically triggers chromatin remodeling. Structure-function evaluation of MBPs with their interaction partners is critical for gaining mechanistic insight into the complex roles of these proteins in mediating cancer epigenetics. It is anticipated that long-term this research will establish the basis for advancing therapeutic design directed toward key MBP regulatory networks/pathways.

Selected Publications

  • Fleming, A. M., Guerra Castañaza Jenkins, B. L., *Buck, B. A., *Burrows, C. J. DNA damage accelerates G-quadruplex folding in a duplex-G-quadruplex-duplex context, JACS, 2024, 146 (16), 11364-11370.

  • Keyes, E. D., Mifflin, M. C., Austin, M. J., Austin, M. J., Alvey, B. J., Lovely, L. H., Smith, A., Rose, T. E., Buck-Koehntop, B. A., Motwani, J., Roberts, A. G. Chemoselective, oxidation-induced macrocyclization of tyrosine-containing peptides, JACS, 2023, 145 (18), 10071-10081. 
  • Sanchez, A., *Buck-Koehntop, B. A., *Miller, K. A. Joining the PARty: PARP Regulation of KDM5A during DNA Repair (and Transcription?), BioEssays, 2022, 44(7), 2200015.
  • Kumbhar, R., Sanchez, A., Perren, J., Gong, F., Corujo, D., Medina, F., Devanathan, S. K., Xhemalce, B., Matouschek, A., Buschbeck, M., Buck-Koehntop, B. A., Miller, K. M. Poly(ADP-ribose)-binding and macroH2A mediate recruitment and functions of KDM5A at DNA lesions, J. Cell. Biol., 2021, 220 (7), e202006149.
  • Hodges, A. J., Hudson, N. O., Buck-Koehntop, B. A. Cys2His2 zinc finger methyl-CpG binding proteins: Getting a handle on methylated DNA, J. Mol. Biol., 2020, 432, 1640-1660.
  • Hudson, N. O., Whitby, F. G., Buck-Koehntop, B. A. Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38, J. Biol. Chem., 2018, 293,  19835-19843.
  • Hudson, N. O., Buck-Koehntop, B. A. Zinc Finger Readers of Methylated DNA, Molecules, 2018, 23 (10), 2555.
  • Pozner, A., Hudson, N. O., Trewhella, J., Terooatea, T. W., Miller, S. A., Buck-Koehntop, B. A. The C-terminal Zinc Fingers of ZBTB38 are Novel Selective Readers of DNA Methylation, J. Mol. Biol., 2018, 430 (3), 258-271 (https://doi.org/10.1016/j.jmb.2017.12.014).
  • Pozner, A.; Terooatea, T. W.; Buck-Koehntop, B. A. Cell Specific Kaiso (ZBTB33) Regulation of Cell Cycle Through cyclin D1 and cyclin E1, J. Biol. Chem., 2016, 291 (47), 24538-24550.
  • Terooatea, T. W.; Pozner, A.; Buck-Koehntop, B. A. PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond.Nucleic Acids Res., 2016, 44 (21), e159.
  • Buck-Koehntop, B. A.; Defossez, P.-A. On how Mammalian Transcription Factors Recognize Methylated DNA. Epigenetics2013, 8, 131-137
  • Buck-Koehntop, B. A.; Stanfield, R. L.; Ekiert, D. C.; Martinez-Yamout, M. A.; Dyson, H. J.; Wilson, I. A.; Wright, P. E. Molecular Basis for Recognition of Methylated and Specific DNA Sequences by the Zinc Finger Protein Kaiso. Proc. Nat. Acad. Sci.2012, 109, 15229-15234.
  • Buck-Koehntop, B. A.; Martinez-Yamout, M. A.; Dyson, H. J.; Wright, P. E. Kaiso uses all Three Zinc Fingers and Adjacent Sequence Motifs for High Affinity Binding to Sequence-specific and Methyl-CpG DNA Targets. FEBS Lett.2012, 586, 734-739.

Last Updated: 6/25/24