June 14, 2019

Kevin Raney, Ph.D.

Professor and Chair
Department of Biochemistry and Molecular Biology
UAMS College of Medicine

Research Interest Statement

The Raney laboratory is interested in the mechanisms and functions of nucleic acid enzymes called helicases. Helicases play central roles in all aspects of DNA and RNA metabolism; therefore they are key enzymes in maintaining genomic stability. Genetic mutations in many helicases have been correlated with numerous cancers. The Pif1 helicase is a major focus of study. Mutations in Pif1 have been linked to increased incidence of breast cancer. We are studying how such mutations alter the biochemical mechanism and ultimately biological function of the enzyme, thereby leading to cancer.

A related interest of the Raney lab is in non-canonical structures of DNA and RNA that form in guanine-rich sequences termed G-quadruplex. Over 500,000 potential G-quadruplex sequences exist in the human genome but their function is largely unknown. We have identified a novel function for G-quadruplex sequences that appears to be fundamental to cellular responses to reactive oxygen species. In response to DNA damage due to oxidative stress, G-quadruplex sequences are removed from the genome, then interact with a variety of proteins. Telomeric and mitochondrial DNA are particularly susceptible to oxidative stress and contain many sequences that readily fold into quadruplex structures. We and others have found that the excised DNA quadruplexes can modulate multiple cellular activities including cell death. We hypothesize that such mechanisms involving G-quadruplexes are important to carcinogenesis. G-quadruplex structures have emerged as a target for developing anti-cancer therapies.

Dr. Raney’s Grants

National Institute of General Medical Sciences

Functions and mechanisms of helicases and g-quadruplex nucleic acids

05/01/2017 – 04/30/2022

$360,000*

*cancer-related annual direct costs

Dr. Raney’s UAMS Collaborators

Robert Eoff, Ph.D., Biochemistry and Molecular Biology

Guilia Baldini, Ph.D., Biochemistry and Molecular Biology

Angus MacNicol, Ph.D., Neurobiology and Developmental Sciences

Alicia Byrd, Ph.D., Biochemistry and Molecular Biology

Boris Zybailov, Ph.D., Biochemistry and Molecular Biology

Stephanie Byrum, Ph.D., Biochemistry and Molecular Biology

Peter Crooks, Ph.D., D.Sc., Pharmaceutical Sciences

Dr. Raney’s External Collaborators

Craig Cameron, Ph.D., Pennsylvania State University

Maria Spies, Ph.D., University of Iowa

Nayun Kim, Ph.D., University of Texas Health Science Center

Opportunities for Collaboration

New ideas emerge from discussions with scientists outside of one’s field. We welcome discussions and will gladly pursue opportunities in areas closely or loosely related to DNA damage response mechanisms. Other areas of interest include drug discovery.

You May Not Know That …

My wife, Veronica, and I have been married for 33 years. We have three children and two grandchildren. I was raised in north Arkansas where I enjoyed canoeing, hiking and caving.

Recent Cancer-Related Publications

  1. Gao J, Byrd AK, Zybailov BL, Marecki JC, Guderyon MJ, Edwards AD, Chib S, West KL, Waldrip ZJ, Mackintosh SG, Gao Z, Putnam AA, Jankowsky E, Raney KD. “DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.” Chem Commun (Camb). 2019, Apr 11;55(31): 4467-4470. doi: 10.1039/c8cc1009h. PMID: 30855040
  2. Marecki JC, Aarattuthodiyil S, Byrd AK, Penthala NR, Crooks PA, Raney KD. “N-Naphthoyl-substituted indole thio-barbituric acid analogs inhibit the helicase activity of the hepatitis C virus NS3”. 2019. Bioorg Med Chem Lett. 2019 Feb 1;29(3):430-434. doi: 10.1016/j.bmcl.2018.12.026. Epub 2018 Dec 13. PMID: 30578035PMCID: PMC6377802 [Available on 2020-02-01]
  3. Griffin, W.C., Gao, J., Byrd, A.K., Chib, S., and Raney, K.D. (2017) “A Biochemical and Biophysical Model of G-quadruplex DNA Recognition by Positive Coactivator of Transcription 4.” J. Biol. Chem. June 9;292(23):9567-9582. PMID: 28416612. PMCID: PMC5465483.
  4. Lopez, C.R., Singh, S., Hambarde, S., Griffin, W.C., Gao, J., Chib, S., Yu, Y., Ira, G., Raney, K.D., and Kim, N. (2017) “Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.” Nucleic Acids Res. 45:5850-5862. PMID: 28369605. PMCID: PMC5449603.
  5. Byrd, A.K., Zybailov, B.L., Maddukuri, L., Gao, J., Marecki, J.C., Jaiswal, M., Bell, M.R., Griffin, W.C., Reed, M.R., Chib, S., Mackintosh, S.G., MacNicol, A.M., Baldini, G., Eoff, R.L., and Raney, K.D., (2016) “Evidence that G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress” J. Biol. Chem. Aug. 19; 291:18041-18057. Doi: 10.1074/jbc.M116.718478. Epub 2016 Jul. 1. PMID: 27369081. PMCID: PMC5016190.
  6. Byrd, A.K. and Raney, K.D., “Structure and function of Pif1 helicase.” 2017. Biochem Soc. Trans. Oct 15;45(5):1159-1171. doi: 10.1042/BST20170096. Epub 2017 Sep 12. Review. PMID: 28900015. PMCID: PMC5870758. DOI: 10.1042/BST20170096