Bio

PhD - University of California, Los Angeles
Postdoctoral - University of Pennsylvania

Research Overview

Research in the Bell lab uses x-ray crystallography and other biochemical and biophysical tools to understand the mechanisms of proteins involved in DNA repair and other important biological processes. One area of interest is E. coli RecA protein, which promotes the central DNA strand-exchange step of DNA repair by homologous recombination. A second project involves the phage-based RecET and RedAB recombination systems, which each consist of a ring-shaped exonuclease (RecE or RedA) that binds to dsDNA ends and processively digests the 5’-ended strand into mononucleotides, and a single strand annealing protein (RecT or RedB), that loads onto the resulting 3’-overhang to promote the annealing of complementary strands. The proteins of these recombination systems are currently being exploited in exciting new methods for genetic engineering and nanopore DNA sequencing, and our research is aimed at providing a structural framework for understanding and re-engineering their functional properties. The structural work is complemented by a thorough structure- function analysis, which involves biochemical and biophysical assays utilizing fluorescence or gel-based methods.

Publications

Recent publications

Korada, S.K.C., Johns, T.D., Smith, C.E., Jones, N.D., McCabe, K.A., and Bell, C.E. (2013) “Crystal structures of Escherichia coli exonuclease I in complex with single stranded DNA provide insights into the mechanism of processive digestion.” Nucleic Acids Res. 41(11), 5887-5897.
Selner, N.G., Luechapanichkul, R., Chen, X., Neel, B.G., Zhang, Z.-Y., Knapp, S., Bell, C.E., and Pei, D. (2014) “Diverse levels of sequence selectivity and catalytic efficiency of protein-tyrosine phosphatases.” Biochemistry 53, 397-412.
Zhang, J., McCabe, K., Bell, C.E. (2011) "Crystal structures of lambda exonuclease in complex with DNA suggest an electrostatic ratchet mechanism for processivity" Proc. Natl. Acad. Sci. USA 108, 11872-11877.
Zhang, Y., Zhang, J., Yuan, C., Hard, R.L., Park, I.-H., Li, C., Bell, C.E., and Pei, D. (2011) "Simultaneous binding of two peptidyl ligands by a Src homology 2 domain" Biochemistry 50, 7637-7646.
Zhang J, Xing X, Herr AB and Bell CE (2009) "Crystal structure of E. coli RecE protein reveals a toroidal tetramer for processing double-stranded DNA breaks" Structure 17(5):690-702.
Gopishetty B, Zhu J, Rajan R, Sobczak AJ, Wnuk SF, Bell CE and Pei D (2009) "Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues" J Am Chem Soc 131(3):1243-50.
Galkin VE, Yu X, Bielnicki J, Ndjonka D, Bell CE and Egelman EH (2009) "Cleavage of bacteriophage lambda cI repressor involves the RecA C-terminal domain" J Mol Biol 385(3):779-87.
Bohl CE, Wu Z, Chen J, Mohler ML, Yang J, Hwang DJ, Mustafa S, Miller DD, Bell CE and Dalton JT (2008) "Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators" Bioorg Med Chem Lett 18(20):5567-70.
Pauff JM, Zhang J, Bell CE and Hille R (2008) "Substrate orientation in xanthine oxidase: crystal structure of enzyme in reaction with 2-hydroxy-6-methylpurine" J Biol Chem 283(8):4818-24.
Bohl CE, Wu Z, Miller DD, Bell CE and Dalton JT (2007) "Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design" J Biol Chem 282(18):13648-55.
Ndjonka D and Bell CE (2006) "Structure of a Hyper-cleavable Monomeric Fragment of Phage Lambda Repressor Containing the Cleavage Site Region" J Mol Biol 362(3):479-89.
Wu Z, Xing X, Bohl CE, Wisler JW, Dalton JT and Bell CE (2006) "Domain structured DNA binding regions of ß protein from Bacteriophage Lambda" J Biol Chem 281(35):25205-14.
Shen G, Rajan R, Zhu J, Bell CE and Pei D (2006) "Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase" J Med Chem 49(10):3003-11.
Rajan R, Wisler JD and Bell CE (2006) "Probing the DNA sequence specificity of Escherichia coli RECA protein" Nucleic Acids Res 34(8):2463-71.
Wilson RC, Bohlen CJ, Foster MP and Bell CE (2006) "Structure of Pfu Pop5, an archaeal RNase P protein" Proc Natl Acad Sci USA 103(4):873-8.
Bell CE (2005) MicroReview: "Structure and mechanism of Escherichia coli RecA ATPase" Mol Microbiol 58(2):358-66.
Bohl CE, Gau W, Miller DD, Bell CE and Dalton JT (2005) "Structural basis for antagonism and resistance of bicalutamide in prostate cancer" Proc Natl Acad Sci USA 102(17):6201-6.
Bohl CE, Miller DD, Chen J, Bell CE and Dalton JT (2005) "Structural basis for accommodation of nonsteroidal ligands in the androgen receptor" J Biol Chem 280(45): 37747-54.
Rajan R, Zhu J, Hu, Pei D and Bell CE (2005) "Crystal structure of S ribosylhomocysteinase (LuxS) in complex with a catalytic 2-keystone intermediate" Biochemistry 44(10):3745-53.