Professor and ChairPicture of Dr. Raney

Member Winthrop P. Rockefeller Cancer Institute

Ph.D., Vanderbilt University, Nashville TN
B.A., Hendrix College, Conway, AR

Office:  (501) 686-5244 – Biomedical Research Center B405B
Labs:  (501) 686-7254 – Biomedical Research Center 2, 421-2, 433-2, 419-2 and 417-2
FAX:  (501) 686-8169

DNA and RNA Metabolism

My laboratory is interested in the enzymology and chemistry of nucleic acid enzymes.  Helicases are enzymes that manipulate DNA and RNA in all aspects of nucleic acid metabolism.  We are studying a DNA helicase from Bacteriophage T4 called Dda (for DNA-Dependent-ATPase) in order to develop a detailed chemical and kinetic mechanism for DNA unwinding by this model DNA helicase.  A second enzyme we study is called Pif1.  This helicase is involved in many aspects of DNA metabolism ranging from telomere maintenance to transcription.  Pif1 binds tightly to unusual DNA structures called quadruplexes, for which the biological functions are being intensively explored.  A second project involves the Hepatitis C viral helicase NS3 (Non-Structural Protein 3).  NS3 is an RNA helicase that is capable of unwinding DNA.  We are studying the mechanism of NS3 as well as its interactions with other HCV and cellular proteins.  Our goal is to recapitulate RNA replication in vitro using biological relevant substrates and proteins and a biologically relevant sub-genomic replicon of HCV.  Our research projects are currently expanding in development of new tools for studying and protein-protein interactions and post-translational modifications at specific sites in the genome using a Crispr-based approach coupled with protein mass spectrometry.  In a new project, we have recently discovered a possible signaling mechanism by which cells respond to DNA damage.  During oxidative stress, guanine residues are oxidized, leading to excision of the damaged DNA.  When the excised DNA consists of specific sequences containing runs of guanine, the resulting DNA fragment can fold into a stable structure called quadruplex DNA.  Telomeric DNA is particularly susceptible to oxidative stress and contains sequences that readily fold into quadruplex structures. The excised DNA quadruplexes can bind to proteins such as DHX36 (a helicase), leading to formation of sub-organelles called stress granules.  The functional role of stress granules is to modulate translation.  Hence, this mechanism provides a stepwise mechanism for the cell to respond to DNA damage leading to changes in translation.


Lab Members

See Dr. Raney’s student, Andrea Edwards, present a Three Minute Thesis.


Selected Publications

Byrd AK, Zybailov BL, Maddukuri L, Gao J, Marecki JC, Jaiswal M, Bell MR, Griffin WC, Reed MR, Chib S, Mackintosh SG, MacNicol AM, Baldini G, Eoff RL, Raney KD. (2016) “Evidence that G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress.” J Biol Chem. Jul 1. pii: jbc.M116.718478. [Epub ahead of print] PMID: 27369081 [Abstract]

Zybailov BL, Byrd AK, Glazko GV, Rahmatallah Y, Raney KD. (2016) “Protein-protein interaction analysis for functional characterization of helicases.” Methods. Apr 20  pii: S1046-2023(16)30087-1. doi: 10.1016/j.ymeth.2016.04.014. (epub ahead of print). PMID:27090004 [Abstract]

Chib, S., Byrd, A.K., and Raney, K.D. (2016) “Yeast Helicase Pif1 unwinds RNA:DNA hybrids with higher processivity than DNA:DNA Duplexes” J. Biol. Chem. 291(11):5889-901. PMID: 26733194  [Abstract]

Zybailov B, Gokulan K, Wiese J, Ramanagoudr-Bhojappa R, Byrd AK, Glazko G, Jaiswal M, Mackintosh S, Varughese KI, Raney KD. (2015) “Analysis of Protein-protein Interaction Interface between Yeast Mitochondrial Proteins Rim1 and Pif1 Using Chemical Cross-linking Mass Spectrometry.” J Proteomics Bioinform. Nov;8(11):243-252. PMID:26807012 [Abstract]

Byrd AK, Raney KD. (2015) “Fine tuning of a DNA fork by the RecQ helicase.” Proc Natl Acad Sci U S A. 112(50):15263-4. PMID:26582797. [Abstract]

Reynolds, K.A., Cameron, C.E., and Raney, K.D. (2015) “Melting of Duplex DNA in the Absence of ATP by the NS3 Helicase Domain through Specific Interaction with a Single-Strand/Double-Strand Junction” Biochemistry, 54(27):4248-4258, DOI: 10.1021/acs.biochem.5b00214, PMID:26582797 [Abstract]

Gao, J., Zybailov, B.L., Byrd, A.K., Griffin, W.C., Chib, S., Mackintosh, S.G., Tackett, A.J., and Raney, K.D., (2015) “Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA” Chem. Commun (Camb). 51(33):7242-7244. PMID: 25813861. [Abstract]

Byrd, A.K. and Raney, K.D. (2015) “A parallel quadruplex DNA is bound tightly but unfolded slowly by Pif1 helicase” J. Biol. Chem. 290(10):6482-94 PMID:25589786. [Abstract]

Reynolds KA, Raney VM, Raney KD. (2015) “A parallel quadruplex DNA is bound tightly but unfolded slowly by Pif1 helicase” J. Biol. Chem. 1259:275-91. PMID:25589786. [Abstract]

Jaiswal, M., Crabtree, N., Bauer, M.A., Hall, R., Raney, K.D. and Zybailov, B.L. (2014) “XLPM: efficient algorithm for the analysis of protein-protein contacts using chemical cross-linking mass spectrometry” BMC Bioinformatics. 15 Suppl 11:S16. PMID:25350700. [Abstract]

Ramanagoudr-Bhojappa, R., Byrd, A.K., Dahl, C., and Raney, K.D. (2014) “Yeast Pif1 Accelerates Annealing of Complementary DNA Strands” Biochemistry. DOI: 10.1021/bi500746v PMID:25393406. [Abstract]

Aarattuthodiyil, S., Byrd, A.K., and Raney, K.D. (2014) “Simultaneous binding to the tracking strand, displaced strand, and the duplex of a DNA fork enhances unwinding by Dda helicase” Nucleic Acids Res. 42(18):11707-20. PMID:25249618 [Abstract]

Waldrip, Z.J., Byrum, S. D., Storey, A. J., Gao, J., Byrd, A. K., Mackintosh, S. G., Wahls, W.P., Taverna, S.D., Raney, K.D.*, and Tackett, A.J.* (2014) “A CRISPR-based Approach for Proteomic Analysis of a Single Genomic Locus” Epigenetics, 9(9):1207-1211. PMID: 25147920.  [Abstract]* corresponding authors

Raney, K.D. (2014) “Chemical modifications of DNA for study of helicase mechanisms.” Bioorg Med Chem. 22(16):4399-406. PMID:24931273 [Abstract]

Ramanagoudr-Bhojappa R., Chib, S., Byrd, A.K., Pandey, M., Patel, S.S., and Raney, K.D. (2013) “Yeast Pif1 Helicase Exhibits a One-base-pair Stepping Mechanism for Unwinding Duplex DNA” J. Biol. Chem. 288, 16185-16195. PMID:23596008 [Abstract]

Ramanagoudr-Bhojappa, R., Blair, L.P., Tackett, A.J., and Raney, K.D., (2013) “Physical and functional interaction between yeast Pif1 helicase and Rim1 single-stranded DNA binding protein” Nucleic Acids Res. 41, 1029-1046, PMID: 231756612. [Abstract]

Raney KD, Byrd AK, Aarattuthodiyil S. (2013) “Structure and Mechanisms of SF1 DNA Helicases.” Adv Exp Med Biol. 2013;767:17-46. PMID: 23161005 [Abstract]

Raney, V.M., Reynolds, K.A., Harrison, M.K., Harrison, D.K., Cameron, C.E., and Raney, K.D. (2012) “Binding by the Hepatitis C Virus NS3 Helicase Partially Melts Duplex DNA” Biochemistry, PMID: 22916835. [Abstract]

He, X., Byrd, A.K., Yun, M.-K., Pemble, C.W., Harrison, D., Yeruva, L., Dahl, C., Kreuzer, K.N., Raney, K.D., and White, S.W. (2012) “The T4 Phage SF1B Helicase Dda is Structurally Optimized to Perform DNA Strand Separation” Structure. 20(7):1189-200. [Abstract]

Byrd AK, Raney KD. (2012) “Superfamily 2 helicases.” Front Biosci (Landmark Ed). 17:2070-88.PMID:22652765 [Abstract]

Byrd, A.K., Matlock, D.L., Bagchi, D., Aarattuthodiyil, S., Harrison, D.K., Croquette, V., and Raney, K.D. (2012) “Dda Helicase Tightly Couples Translocation on Single-stranded DNA to Unwinding of Duplex DNA: Dda is an Optimally Active Helicase” J. Mol. Biol. 420(3):141-54. PMID: 22504228 [Abstract]

Benkovic SJ, Raney KD. (2011) “Mechanisms: molecular machines.” Curr Opin Chem Biol. 15(5):577-9. PMID: 22504228 [Abstract]

Liu, J., Choi, M., Stanenas, A.G., Byrd, A.K., Raney, K.D., Cohan, C. and Bianco, P.R. (2011) “Novel, fluorescent, SSB protein chimeras with broad utility” Protein Sci. 20, 1005-1020. PMID:21920800. [Abstract]

Hwang, J., Huang, L., Cordek, D.G., Vaughan, R., Reynolds, S.L., Kihara, G., Raney, K.D., Kao, C.C., Cameron, C.E. (2010) “Hepatitis C virus nonstructural protein 5A: biochemical characterization of a novel structural class of RNA-binding proteins” J. Virol. 84, 12480-12491. PMID: 20926572.  [Abstract]

Raney KD, Sharma SD, Moustafa IM, Cameron CE. (2010) “Hepatitis C virus non-structural protein 3 (HCV NS3): a multifunctional antiviral target.”J Biol Chem. 285(30):22725-31. PMID:20457607.  [Abstract]

Eoff, R.L., and Raney, K.D. (2010) “Kinetic Mechanism for DNA unwinding by Multiple Molecules of Dda Helicase Aligned on DNA” Biochemistry, 49, 4543-4553. PMID:20408588 [Abstract]

Matlock, D.L., Yeruva, L., Byrd, A.K., Mackintosh, S.G., Langston, C., Brown, C., Cameron, C.E., Fischer, C.J., and Raney, K.D. (2010) Investigation of translocation, DNA unwinding, and protein displacement by NS3h, the helicase domain from the hepatitis C virus helicase” Biochemistry, 49, 2097-2109. PMID:20108974 [Abstract]

Wang, X., Arnold, J.J., Uchida, A., Raney, K.D., and Cameron, C.E. (2010) “Phosphate release contributes to the rate-limiting step for unwinding by an RNA helicase” Nucleic Acids Res. 38, 1312-1324. PMID:19969541 [Abstract]


Complete List of Published Work in My Bibliography