Brandt F. Eichman, Ph.D.
Associate Professor of Biological Sciences
Associate Professor of Biochemistry
Vanderbilt University Medical Center
5270A MRB III, 465 21st Ave. S.
Nashville, TN 37232
DNA damage arising from exposure to environmental toxins and cellular metabolites thwarts DNA replication and leads to genome instability, cell death, and diseases including cancer. Our laboratory uses the tools of structural biology and biochemistry to investigate molecular mechanisms of proteins involved in repairing DNA damage and maintaining replication fork progression. We primarily use X-ray crystallography as a starting point to understand how these proteins recognize and manipulate DNA structure to carry out their particular functions. Current work focuses on base excision repair of DNA alkylation damage by DNA glycosylases, repair of stalled replication forks by structure-specific DNA translocases, and the coordination of DNA unwinding and synthesis during eukaryotic replication. The long-term goals are to understand the fundamental processes underlying genome maintenance and to develop new therapeutic strategies that target genetic diseases.
- Mullins, EA, Shi, R, Kotsch, LA, Eichman, BF A New Family of HEAT-Like Repeat Proteins Lacking a Critical Substrate Recognition Motif Present in Related DNA Glycosylases. PLoS One, 10(5), e0127733, 2015.
- Szulik, MW, Pallan, PS, Nocek, B, Voehler, M, Banerjee, S, Brooks, S, Joachimiak, A, Egli, M, Eichman, BF, Stone, MP Differential stabilities and sequence-dependent base pair opening dynamics of Watson-Crick base pairs with 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxylcytosine. Biochemistry, 54(5), 1294-305, 2015.
- Kile, AC, Chavez, DA, Bacal, J, Eldirany, S, Korzhnev, DM, Bezsonova, I, Eichman, BF, Cimprich, KA HLTF''s Ancient HIRAN Domain Binds 3'' DNA Ends to Drive Replication Fork Reversal. Mol Cell, 58(6), 1090-100, 2015.
- Mullins, EA, Shi, R, Parsons, ZD, Yuen, PK, David, SS, Igarashi, Y, Eichman, BF The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions. Nature, 2015.
- Brooks, SC, Fischer, RL, Huh, JH, Eichman, BF 5-Methylcytosine Recognition by Arabidopsis thaliana DNA Glycosylases DEMETER and DML3. Biochemistry, 53(15), 2525-2532, 2014.
- Mason, AC, Rambo, RP, Greer, B, Pritchett, M, Tainer, JA, Cortez, D, Eichman, BF A structure-specific nucleic acid-binding domain conserved among DNA repair proteins. Proc Natl Acad Sci U S A, 1117618-7623, 2014.
- Jang, H, Shin, H, Eichman, BF, Huh, JH Excision of 5-hydroxymethylcytosine by DEMETER family DNA glycosylases. Biochem Biophys Res Commun, 446(4), 41067-72, 2014.
- Vaithiyalingam, S, Arnett, DR, Aggarwal, A, Eichman, BF, Fanning, E, Chazin, WJ Insights into Eukaryotic Primer Synthesis from Structures of the p48 Subunit of Human DNA Primase. J Mol Biol, 426558-69, 2014.
- Troll, CJ, Adhikary, S, Cueff, M, Mitra, I, Eichman, BF, Camps, M Interplay between base excision repair activity and toxicity of 3-methyladenine DNA glycosylases in an E. coli complementation system. Mutat Res, 763-76464-73, 2014.
- Feldkamp, MD, Mason, AC, Eichman, BF, Chazin, WJ Structural Analysis of Replication Protein A Recruitment of the DNA Damage Response Protein SMARCAL1. Biochemistry, 533052-3061, 2014.
- Mullins, EA, Rubinson, EH, Eichman, BF The substrate binding interface of alkylpurine DNA glycosylase AlkD. DNA Repair (Amst), 1350-54, 2014.
- Mullins, EA, Rubinson, EH, Pereira, KN, Wade Calcutt, M, Christov, PP, Eichman, BF An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated base excision repair products. Methods, 64(1), 59-66, 2013.
- Rubinson, EH, Christov, PP, Eichman, BF Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone. Biochemistry, 52(42), 7363-5, 2013.
- Du, W, Josephrajan, A, Adhikary, S, Bowles, T, Bielinsky, AK, Eichman, BF Mcm10 self-association is mediated by an N-terminal coiled-coil domain. PLoS One, 8(7), e70518, 2013.
- Adhikary, S, Cato, MC, McGary, KL, Rokas, A, Eichman, BF Non-productive DNA damage binding by DNA glycosylase-like protein Mag2 from Schizosaccharomyces pombe. DNA Repair (Amst), 12196-204, 2013.
- Brooks, SC, Adhikary, S, Rubinson, EH, Eichman, BF Recent advances in the structural mechanisms of DNA glycosylases. Biochim Biophys Acta, 1834(1), 247-71, 2013.
- Betous, R, Couch, FB, Mason, AC, Eichman, BF, Manosas, M, Cortez, D Substrate-Selective Repair and Restart of Replication Forks by DNA Translocases. Cell Rep, 31-12, 2013.
- Shi, M, Pedchenko, V, Greer, BH, Van Horn, WD, Santoro, SA, Sanders, CR, Hudson, BG, Eichman, BF, Zent, R, Pozzi, A Enhancing integrin alpha1 I-domain affinity to ligand potentiates integrin alpha1beta1-mediated downregulation of collagen synthesis. J Biol Chem, 28735139-35152, 2012.
- Rubinson, EH, Eichman, BF Nucleic acid recognition by tandem helical repeats. Curr Opin Struct Biol, 22(1), 101-9, 2012.
- Betous, R, Mason, AC, Rambo, RP, Bansbach, CE, Badu-Nkansah, A, Sirbu, BM, Eichman, BF, Cortez, D SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication. Genes Dev, 26(2), 151-62, 2012.
- Du, W, Stauffer, ME, Eichman, BF Structural biology of replication initiation factor Mcm10. Subcell Biochem, 62197-216, 2012.
- Adhikary, S, Eichman, BF Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine DNA glycosylase. EMBO Rep, 12(12), 1286-92, 2011.
- Camps, M, Eichman, BF Unraveling a connection between DNA demethylation repair and cancer. Mol Cell, 44(3), 343-4, 2011.
- Rubinson, EH, Gowda, AS, Spratt, TE, Gold, B, Eichman, BF An unprecedented nucleic acid capture mechanism for excision of DNA damage. Nature, 468(7322), 406-11, 2010.
- Mok, YG, Uzawa, R, Lee, J, Weiner, GM, Eichman, BF, Fischer, RL, Huh, JH Domain structure of the DEMETER 5-methylcytosine DNA glycosylase. Proc Natl Acad Sci U S A, 107(45), 19225-30, 2010.
- Vaithiyalingam, S, Warren, EM, Eichman, BF, Chazin, WJ Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase. Proc Natl Acad Sci U S A, 107(31), 13684-9, 2010.
- Robertson, PD, Chagot, B, Chazin, WJ, Eichman, BF Solution NMR structure of the C-terminal DNA binding domain of Mcm10 reveals a conserved MCM motif. J Biol Chem, 285(30), 22942-9, 2010.
- Rubinson, EH, Adhikary, S, and Eichman, BF Structural Studies of Alkylpurine DNA Glycosylases. ACS Symposium Series : Structural Biology of DNA Damage and Repair., 104129-45, 2010.
- Warren, EM, Huang, H, Fanning, E, Chazin, WJ, Eichman, BF Physical interactions between MCM10, DNA, AND DNA polymerase alpha. J Biol Chem, 284(36), 24662-24672, 2009.
- Rubinson, EH, Metz, AH, O'Quin, J, Eichman, BF A new protein architecture for processing alkylation damaged DNA: the crystal structure of DNA glycosylase AlkD. J Mol Biol, 381(1), 13-23, 2008.
- Robertson, PD*, Warren, EM*, Zhang, H*, Friedman, DB, Lary, JW, Cole, JL, Tutter, AV, Walter, JC, Fanning, E, Eichman, BF Domain architecture and biochemical characterization of vertebrate Mcm10. J Biol Chem, 283(6), 3338-48, 2008.
- Warren, EM, Vaithiyalingam, S, Haworth, J, Greer, B, Bielinsky, AK, Chazin, WJ, Eichman, BF Structural basis for DNA binding by replication initiator mcm10. Structure, 16(12), 1892-901, 2008.
- Bowles, T*, Metz, AH*, O'Quin, J, Wawrzak, Z, Eichman, BF Structure and DNA binding of alkylation response protein AidB. Proc Natl Acad Sci U S A, 105(40), 15299-15304, 2008.
- Metz, AH, Hollis, T, Eichman, BF DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG). EMBO J, 26(9), 2411-20, 2007.
- Brieba, Luis G, Eichman, Brandt F, Kokoska, Robert J, Doublie, Sylvie, Kunkel, Tom A, Ellenberger, Tom Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase. EMBO J, 23(17), 3452-3461, 2004.
- Eichman BF, Fanning E The power of pumping together; deconstructing the engine of a DNA replication machine. Cell, 119(1), 3-4, 2004.
- Eichman, BF, Fanning, E The power of pumping together; deconstructing the engine of a DNA replication machine. Cell, 119(1), 3-4, 2004.
- Eichman, Brandt F, O''Rourke, Eyleen J, Radicella, J Pablo, Ellenberger, Tom Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases. EMBO J, 22(19), 4898-909, 2003.
- Eichman, Brandt F, Ortiz-Lombardia, Miguel, Aymami, Joan, Coll, Miquel, Ho, Pui Shing The inherent properties of DNA four-way junctions: comparing the crystal structures of holliday junctions. J Mol Biol, 320(5), 1037-51, 2002.
- Ho, P S, Eichman, B F The crystal structures of DNA Holliday junctions. Curr Opin Struct Biol, 11(3), 302-8, 2001.
- Eichman, B F, Mooers, B H, Alberti, M, Hearst, J E, Ho, P S The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions. J Mol Biol, 308(1), 15-26, 2001.
- Eichman, B F, Vargason, J M, Mooers, B H, Ho, P S The Holliday junction in an inverted repeat DNA sequence: sequence effects on the structure of four-way junctions. Proc Natl Acad Sci U S A, 97(8), 3971-6, 2000.
- Vargason, J M, Eichman, B F, Ho, P S The extended and eccentric E-DNA structure induced by cytosine methylation or bromination. Nat Struct Biol, 7(9), 758-61, 2000.
- Eichman, B F, Schroth, G P, Basham, B E, Ho, P S The intrinsic structure and stability of out-of-alternation base pairs in Z-DNA. Nucleic Acids Res, 27(2), 543-50, 1999.
- Basham, B, Eichman, BF, and Ho, PS "The single crystal structures of Z-DNA." In Neidle, S (ed.), The Oxford Handbook of Nucleic Acid Structure. Oxford University Press, Oxford, UK, 1(), 199-252, 1999.
- Mooers, B H, Eichman, B F, Ho, P S The structures and relative stabilities of d(G x G) reverse Hoogsteen, d(G x T) reverse wobble, and d(G x C) reverse Watson-Crick base-pairs in DNA crystals. J Mol Biol, 269(5), 796-810, 1997.