Center for Matrix Biology - Vanderbilt University and Medical Center

Brandt F. Eichman, Ph.D.
Assistant Professor in the Department of Biological Sciences

	Office Address:	Department of Biological Sciences, Vanderbilt University
	Mailing Address:	Department of Biological Sciences, Vanderbilt University Nashville, TN 37235-1634
	Lab address:	MRBIII U5221/U5217
	Phone:	(615) 936-5233
		email \| website

Brandt F. Eichman, Ph.D.
Assistant Professor in the Department of Biological Sciences

	Office Address:	Department of Biological Sciences, Vanderbilt University
	Mailing Address:	Department of Biological Sciences, Vanderbilt University Nashville, TN 37235-1634
	Lab address:	MRBIII U5221/U5217
	Phone:	(615) 936-5233
		email \| website

Secondary appointment in the Biochemistry department.

Research Summary

Research in my laboratory is focused on understanding how proteins recognize and manipulate DNA structure during replication and repair processes. We use X-ray crystallography and biochemistry to investigate the physical and mechanistic basis for the biological functions of several DNA processing enzymes.

A major focus in the lab is to understand how DNA replication is initiated in eukaryotes. Specifically, we are interested in the mechanism of replication fork assembly at the molecular level. The initiation of DNA replication in eukaryotic cells is highly regulated and is essential for maintenance of genome integrity. Failure to copy the genome only once and at the proper time during the cell cycle can lead to elevated mutation rates, chromosome instability, and the development of cancer. This process involves a choreographed assembly of several dynamic protein complexes which must recognize and unwind DNA at origins of replication, interpret cell cycle signals, and ultimately result in the formation of active replication forks. We are currently working to determine the crystal structures of several initiation proteins which are required for DNA unwinding and loading DNA polymerases onto chromatin. Using a combination of structural, biophysical, biochemical, and biological approaches, we aim to generate a comprehensive model for the spatial arrangement of these proteins during DNA unwinding in an effort to understand the molecular mechanism of replication initiation.

A second area of research is aimed at understanding how proteins recognize and repair damaged DNA. The stability of the genome is constantly challenged by the chemical reactivity of DNA bases, which are subject to modifications by cellular and environmental agents. These chemical modifications can cause DNA mutations or inhibit replication and thereby cause toxicity or disease. It is therefore important to understand the the basis for recognition of structural damage to DNA by repair proteins. DNA glycosylases locate and remove damaged bases from the DNA backbone and are specific to a particular type of modification. The importance of the substrate specificities of these enzymes is underscored by the fact that glycosylases must identify subtle changes in the DNA structure amidst a vast excess of unmodified DNA. We are studying the structural aspects of how DNA glycosylases recognize and remove alkylated bases from DNA.

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Associated initiative(s):

Career opportunities:
Postdoctoral Position Available

Selected Publications

» Warren, EM, Huang, H, Fanning, E, Chazin, WJ, Eichman, BF Physical interactions between MCM10, DNA, AND DNA polymerase alpha J Biol Chem 2009. 284:24662-24672

» 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 2008. 105:15299-15304

» 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. 16:1892-901

» 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 2008. 283:3338-48

» 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 2008. 381:13-23

» Metz, AH, Hollis, T, Eichman, BF DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG) EMBO J 2007. 26:2411-20

» 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 2004. 23:3452-3461

» Eichman, BF, Fanning, E The power of pumping together; deconstructing the engine of a DNA replication machine Cell 2004. 119:3-4

» 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 2003. 22:4898-909

» 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 2002. 320:1037-51

» 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 2001. 308:15-26

» Ho, P S, Eichman, B F The crystal structures of DNA Holliday junctions Curr Opin Struct Biol 2001. 11:302-8

» 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 2000. 7:758-61

» 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 2000. 97:3971-6

» 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 1999. 1:199-252

» 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 1999. 27:543-50

» 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 1997. 269:796-810