Brandt F. Eichman, Ph.D.

Professor

brandt.eichman@vanderbilt.edu

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Faculty Appointments
Professor of Biological Sciences Associate Professor of Biochemistry
Education
Ph.D., Biochemistry & Biophysics, Oregon State University, Corvallis, OregonB.S., University of Mississippi, Oxford, Mississippi
Office Address
Department of Biological Sciences, Vanderbilt University
Box 351634, Station B
Nashville, TN 37235-1634
Research Description
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.
Research Keywords
DNA Repair, DNA Replication, Genome Maintenance, Structural Biology, X-ray Crystallography
Publications
Badu-Nkansah A, Mason AC, Eichman BF, Cortez D. Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3). J. Biol. Chem [print-electronic]. 2016 Apr 4/8/2016; 291(15): 8251-7. PMID: 26884333, PII: M115.709733, DOI: 10.1074/jbc.M115.709733, ISSN: 1083-351X.

Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Christopher Fromme J, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016; 7: 10882. PMID: 26947396, PMCID: PMC4786681, PII: ncomms10882, DOI: 10.1038/ncomms10882, ISSN: 2041-1723.

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 [print-electronic]. 2015 Nov 11/12/2015; 527(7577): 254-8. PMID: 26524531, PII: nature15728, DOI: 10.1038/nature15728, ISSN: 1476-4687.

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 [print-electronic]. 2015 Jun 6/18/2015; 58(6): 1090-100. PMID: 26051180, PMCID: PMC4475461, PII: S1097-2765(15)00349-4, DOI: 10.1016/j.molcel.2015.05.013, ISSN: 1097-4164.

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 [print-electronic]. 2015 Feb 2/10/2015; 54(5): 1294-305. PMID: 25632825, PMCID: PMC4325598, DOI: 10.1021/bi501534x, ISSN: 1520-4995.

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. 2015; 10(5): e0127733. PMID: 25978435, PMCID: PMC4433238, PII: PONE-D-15-08169, DOI: 10.1371/journal.pone.0127733, ISSN: 1932-6203.

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 [print-electronic]. 2014 May 5/27/2014; 111(21): 7618-23. PMID: 24821763, PMCID: PMC4040553, PII: 1324143111, DOI: 10.1073/pnas.1324143111, ISSN: 1091-6490.

Feldkamp MD, Mason AC, Eichman BF, Chazin WJ. Structural analysis of replication protein A recruitment of the DNA damage response protein SMARCAL1. Biochemistry [print-electronic]. 2014 May 5/13/2014; 53(18): 3052-61. PMID: 24730652, PMCID: PMC4020579, DOI: 10.1021/bi500252w, ISSN: 1520-4995.

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 [print-electronic]. 2014 May; 763-764: 64-73. PMID: 24709477, PMCID: PMC4195818, PII: S0027-5107(14)00065-7, DOI: 10.1016/j.mrfmmm.2014.03.007, ISSN: 1873-135X.

Brooks SC, Fischer RL, Huh JH, Eichman BF. 5-methylcytosine recognition by Arabidopsis thaliana DNA glycosylases DEMETER and DML3. Biochemistry [print-electronic]. 2014 Apr 4/22/2014; 53(15): 2525-32. PMID: 24678721, PMCID: PMC4004242, DOI: 10.1021/bi5002294, ISSN: 1520-4995.

Jang H, Shin H, Eichman BF, Huh JH. Excision of 5-hydroxymethylcytosine by DEMETER family DNA glycosylases. Biochem. Biophys. Res. Commun [print-electronic]. 2014 Apr 4/18/2014; 446(4): 1067-72. PMID: 24661881, PII: S0006-291X(14)00503-8, DOI: 10.1016/j.bbrc.2014.03.060, ISSN: 1090-2104.

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 [print-electronic]. 2014 Feb 2/6/2014; 426(3): 558-69. PMID: 24239947, PMCID: PMC3946992, PII: S0022-2836(13)00718-3, DOI: 10.1016/j.jmb.2013.11.007, ISSN: 1089-8638.

Mullins EA, Rubinson EH, Eichman BF. The substrate binding interface of alkylpurine DNA glycosylase AlkD. DNA Repair (Amst.) [print-electronic]. 2014 Jan; 13: 50-4. PMID: 24286669, PMCID: PMC4039204, PII: S1568-7864(13)00266-8, DOI: 10.1016/j.dnarep.2013.10.009, ISSN: 1568-7856.

Mullins EA, Rubinson EH, Pereira KN, Calcutt MW, Christov PP, Eichman BF. An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated base excision repair products. Methods [print-electronic]. 2013 Nov; 64(1): 59-66. PMID: 23876937, PMCID: PMC3812247, PII: S1046-2023(13)00269-7, DOI: 10.1016/j.ymeth.2013.07.020, ISSN: 1095-9130.

Rubinson EH, Christov PP, Eichman BF. Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone. Biochemistry [print-electronic]. 2013 Oct 10/22/2013; 52(42): 7363-5. PMID: 24090276, PMCID: PMC3852881, DOI: 10.1021/bi401195r, ISSN: 1520-4995.

Bétous R, Couch FB, Mason AC, Eichman BF, Manosas M, Cortez D. Substrate-selective repair and restart of replication forks by DNA translocases. Cell Rep [print-electronic]. 2013 Jun 6/27/2013; 3(6): 1958-69. PMID: 23746452, PMCID: PMC3700663, PII: S2211-1247(13)00219-2, DOI: 10.1016/j.celrep.2013.05.002, ISSN: 2211-1247.

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.) [print-electronic]. 2013 Mar 3/1/2013; 12(3): 196-204. PMID: 23273506, PMCID: PMC4008723, PII: S1568-7864(12)00290-X, DOI: 10.1016/j.dnarep.2012.12.001, ISSN: 1568-7856.

Brooks SC, Adhikary S, Rubinson EH, Eichman BF. Recent advances in the structural mechanisms of DNA glycosylases. Biochim. Biophys. Acta [print-electronic]. 2013 Jan; 1834(1): 247-71. PMID: 23076011, PMCID: PMC3530658, PII: S1570-9639(12)00246-4, DOI: 10.1016/j.bbapap.2012.10.005, ISSN: 0006-3002.

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 [electronic-print]. 2013; 8(7): e70518. PMID: 23894664, PMCID: PMC3720919, PII: PONE-D-13-21329, DOI: 10.1371/journal.pone.0070518, ISSN: 1932-6203.

Shi M, Pedchenko V, Greer BH, Van Horn WD, Santoro SA, Sanders CR, Hudson BG, Eichman BF, Zent R, Pozzi A. Enhancing integrin a1 inserted (I) domain affinity to ligand potentiates integrin a1ß1-mediated down-regulation of collagen synthesis. J. Biol. Chem [print-electronic]. 2012 Oct 10/12/2012; 287(42): 35139-52. PMID: 22888006, PMCID: PMC3471707, PII: M112.358648, DOI: 10.1074/jbc.M112.358648, ISSN: 1083-351X.

Rubinson EH, Eichman BF. Nucleic acid recognition by tandem helical repeats. Curr. Opin. Struct. Biol [print-electronic]. 2012 Feb; 22(1): 101-9. PMID: 22154606, PMCID: PMC3766767, PII: S0959-440X(11)00199-0, DOI: 10.1016/j.sbi.2011.11.005, ISSN: 1879-033X.

Bétous 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. 2012 Jan 1/15/2012; 26(2): 151-62. PMID: 22279047, PMCID: PMC3273839, PII: 26/2/151, DOI: 10.1101/gad.178459.111, ISSN: 1549-5477.

Du W, Stauffer ME, Eichman BF. Structural biology of replication initiation factor Mcm10. Subcell. Biochem. 2012; 62: 197-216. PMID: 22918587, DOI: 10.1007/978-94-007-4572-8_11, ISSN: 0306-0225.

Adhikary S, Eichman BF. Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine DNA glycosylase. EMBO Rep. 2011 Dec; 12(12): 1286-92. PMID: 21960007, PMCID: PMC3245690, PII: embor2011189, DOI: 10.1038/embor.2011.189, ISSN: 1469-3178.

Camps M, Eichman BF. Unraveling a connection between DNA demethylation repair and cancer. Mol. Cell. 2011 Nov 11/4/2011; 44(3): 343-4. PMID: 22055180, PII: S1097-2765(11)00808-2, DOI: 10.1016/j.molcel.2011.10.009, ISSN: 1097-4164.

Rubinson EH, Gowda AS, Spratt TE, Gold B, Eichman BF. An unprecedented nucleic acid capture mechanism for excision of DNA damage. Nature [print-electronic]. 2010 Nov 11/18/2010; 468(7322): 406-11. PMID: 20927102, PMCID: PMC4160814, PII: nature09428, DOI: 10.1038/nature09428, ISSN: 1476-4687.

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 [print-electronic]. 2010 Nov 11/9/2010; 107(45): 19225-30. PMID: 20974931, PMCID: PMC2984145, PII: 1014348107, DOI: 10.1073/pnas.1014348107, ISSN: 1091-6490.

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 [print-electronic]. 2010 Aug 8/3/2010; 107(31): 13684-9. PMID: 20643958, PMCID: PMC2922289, PII: 1002009107, DOI: 10.1073/pnas.1002009107, ISSN: 1091-6490.

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 [print-electronic]. 2010 Jul 7/23/2010; 285(30): 22942-9. PMID: 20489205, PMCID: PMC2906287, PII: M110.131276, DOI: 10.1074/jbc.M110.131276, ISSN: 1083-351X.

Rubinson, EH, Adhikary, S, and Eichman, BF. ACS Symposium Series : Structural Biology of DNA Damage and Repair. [place unknown: publisher unknown]; 2010. (1041). Available from: http://pubs.acs.org/doi/full/10.1021/bk-2010-1041.ch003.

Warren EM, Huang H, Fanning E, Chazin WJ, Eichman BF. Physical interactions between Mcm10, DNA, and DNA polymerase alpha. J. Biol. Chem [print-electronic]. 2009 Sep 9/4/2009; 284(36): 24662-72. PMID: 19608746, PMCID: PMC2782055, PII: M109.020438, DOI: 10.1074/jbc.M109.020438, ISSN: 0021-9258.

Warren EM, Vaithiyalingam S, Haworth J, Greer B, Bielinsky AK, Chazin WJ, Eichman BF. Structural basis for DNA binding by replication initiator Mcm10. Structure. 2008 Dec 12/10/2008; 16(12): 1892-901. PMID: 19081065, PMCID: PMC2636851, PII: S0969-2126(08)00383-3, DOI: 10.1016/j.str.2008.10.005, ISSN: 0969-2126.

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 [print-electronic]. 2008 Oct 10/7/2008; 105(40): 15299-304. PMID: 18829440, PMCID: PMC2563087, PII: 0806521105, DOI: 10.1073/pnas.0806521105, ISSN: 1091-6490.

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 [print-electronic]. 2008 Aug 8/1/2008; 381(1): 13-23. PMID: 18585735, PMCID: PMC3763988, PII: S0022-2836(08)00671-2, DOI: 10.1016/j.jmb.2008.05.078, ISSN: 1089-8638.

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 [print-electronic]. 2008 Feb 2/8/2008; 283(6): 3338-48. PMID: 18065420, PMCID: PMC2753450, PII: M706267200, DOI: 10.1074/jbc.M706267200, ISSN: 0021-9258.

Metz AH, Hollis T, Eichman BF. DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG). EMBO J [print-electronic]. 2007 May 5/2/2007; 26(9): 2411-20. PMID: 17410210, PMCID: PMC1864966, PII: 7601649, DOI: 10.1038/sj.emboj.7601649, ISSN: 0261-4189.

Eichman BF, Fanning E. The power of pumping together; deconstructing the engine of a DNA replication machine. Cell. 2004 Oct 10/1/2004; 119(1): 3-4. PMID: 15454074, PII: S0092867404008967, DOI: 10.1016/j.cell.2004.09.023, ISSN: 0092-8674.

Brieba LG, Eichman BF, Kokoska RJ, Doublié S, Kunkel TA, Ellenberger T. Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase. EMBO J [print-electronic]. 2004 Sep 9/1/2004; 23(17): 3452-61. PMID: 15297882, PMCID: PMC516626, PII: 7600354, DOI: 10.1038/sj.emboj.7600354, ISSN: 0261-4189.

Eichman BF, Fanning E. The power of pumping together; deconstructing the engine of a DNA replication machine [editorial]. Cell. 2004; 119((1)): 3-4.

Eichman BF, O'Rourke EJ, Radicella JP, Ellenberger T. Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases. EMBO J. 2003 Oct 10/1/2003; 22(19): 4898-909. PMID: 14517230, PMCID: PMC204488, DOI: 10.1093/emboj/cdg505, ISSN: 0261-4189.

Eichman BF, Ortiz-Lombardía M, Aymamí J, Coll M, Ho PS. The inherent properties of DNA four-way junctions: comparing the crystal structures of holliday junctions. J. Mol. Biol. 2002 Jul 7/26/2002; 320(5): 1037-51. PMID: 12126623, PMCID: PMC4537162, PII: S0022283602005405, ISSN: 0022-2836.

Ho PS, Eichman BF. The crystal structures of DNA Holliday junctions. Curr. Opin. Struct. Biol. 2001 Jun; 11(3): 302-8. PMID: 11406378, PII: S0959-440X(00)00219-0, ISSN: 0959-440X.

Eichman BF, Mooers BH, Alberti M, Hearst JE, Ho PS. The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions. J. Mol. Biol. 2001 Apr 4/20/2001; 308(1): 15-26. PMID: 11302703, PII: S0022-2836(01)94567-X, DOI: 10.1006/jmbi.2001.4567, ISSN: 0022-2836.

Vargason JM, Eichman BF, Ho PS. The extended and eccentric E-DNA structure induced by cytosine methylation or bromination. Nat. Struct. Biol. 2000 Sep; 7(9): 758-61. PMID: 10966645, DOI: 10.1038/78985, ISSN: 1072-8368.

Eichman BF, Vargason JM, Mooers BH, Ho PS. 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. 2000 Apr 4/11/2000; 97(8): 3971-6. PMID: 10760268, PMCID: PMC18126, PII: 97/8/3971, ISSN: 0027-8424.

Eichman BF, Schroth GP, Basham BE, Ho PS. The intrinsic structure and stability of out-of-alternation base pairs in Z-DNA. Nucleic Acids Res. 1999 Jan 1/15/1999; 27(2): 543-50. PMID: 9862978, PMCID: PMC148213, PII: gkc118, ISSN: 0305-1048.

Basham, B, Eichman, BF, and Ho, PS. In Neidle, S (ed.), The Oxford Handbook of Nucleic Acid Structure. Oxford University Press, Oxford, UK. [place unknown: publisher unknown]; 1999. (1).

Mooers BH, Eichman BF, Ho PS. 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. 1997 Jun 6/27/1997; 269(5): 796-810. PMID: 9223642, PII: S0022283697911001, ISSN: 0022-2836.

Available Postdoctoral Position Details
Posted: 8/19/2016

Postdoctoral positions are available to study the structures and molecular mechanisms of proteins involved in progression and maintenance of eukaryotic DNA replication forks and repair of DNA alkylation damage. 

 A Ph.D. in biochemistry, biophysics, structural biology or related field and at least one first-author publication are required. Experience in X-ray crystallography, electron microscopy, and insect and mammalian cell expression systems is highly desirable.

To apply, please email CV, a cover letter describing why you are interested in the lab, reprints of recent publications, and names of 3 references to Brandt Eichman (brandt.eichman@vanderbilt.edu).

Lab webpage: http://structbio.vanderbilt.edu/eichman/