Brandt F. Eichman, Ph.D.

Assistant Professor of Biological Sciences
Ph.D., Oregon State University, 2000 (Biochemistry & Biophysics)

This laboratory uses structural and biochemical approaches to investigate proteins involved in genome maintenance. The overall goal is to understand how DNA repair and replication proteins manipulate nucleic acid structure in order to develop new therapeutic strategies targeted at cancer and heritable diseases. One major focus is to understand the mechanisms of enzymes that repair damaged DNA. Chemical modifications to DNA bases by cellular and environmental alkylating agents cause mutations or inhibit replication and thereby cause toxicity or disease. The structures and functions of DNA glycosylases are being studied to determine how these enzymes locate and remove alkylated bases from DNA. A second aim is to understand the molecular mechanism of eukaryotic DNA replication initiation, which involves a choreographed assembly of 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. Using a combination of X-ray crystallography, NMR, and enzymology, this research aims to generate a comprehensive model for the spatial arrangement of these proteins in an effort to understand how the replisome is assembled and regulated.

Recent Publications

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.

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. 2008 283:3338-48.

Bowles T, Metz AH, O'Quin J, Wawrzak Z, Eichman BF. Structure and DNA binding of alkylation response protein AidB. Proc Natl Acad Sci USA. 2008 105:15299-15304.

Warren EM, Vaithiyalingam S, Haworth J, Greer B, Bielinsky A-K, Chazin WJ, Eichman BF. Structural basis for DNA binding by replication initiator Mcm10. Structure. 2008 16:1892-1901. (**cover article**)

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

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

Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T. Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase. EMBO J. 2004 23:3452-61.

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 22:4898-909.

Eichman BF, Ortiz-Lombardia M, Aymami J, Coll M, Ho PS. The inherent properties of DNA four-way junctions: comparing the crystal structures of holliday junctions. J Mol Biol. 2002 320:1037-51.

Ho PS, Eichman BF. The crystal structures of DNA Holliday junctions. Curr Opin Struct Biol. 2001 11:302-8. Review.

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 308:15-26.

Vargason JM, Eichman BF, Ho PS. The extended and eccentric E-DNA structure induced by cytosine methylation or bromination. Nat Struct Biol. 2000 7:758-61.

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 USA. 2000 97:3971-6.