Eric J. Enemark, Ph.D.
Member Winthrop P. Rockefeller Cancer Institute
Ph.D., Stanford University
B.A., Carleton College
Office: 501-214-2445 – Biomedical Research Center 1 B405C
Lab: Biomedical Research Center 1 B406/B407
DNA replication is a fundamental process for all organisms to precisely duplicate genetic material prior to cell division. Disruption of DNA replication causes genetic instability associated with cancer and other diseases. The central engine that drives the DNA replication machinery of eukaryotes and archaea is a 500 kDa hexameric ring helicase known as the minichromosome maintenance (MCM) complex. In addition to its fundamental role in driving the replication machinery along DNA, the MCM complex also plays a critical role in the controlled initiation of replication. Initiation relies on the dramatic transformation of the core MCM:DNA structure from a two-ring structure that inertly encircles both strands of the DNA double-helix to single rings that each encircle only one strand. The central mystery of this transformation is: How does the excluded strand get outside of the ring? The Enemark lab is investigating this transformation by structural biology approaches, including X-ray crystallography and Cryo-EM.
M. Meagher*, L. B. Epling*, E. J. Enemark, “DNA translocation mechanism of the MCM complex and implications for replication initiation”, Nat Commun., doi: 10.1038/s41467-019-11074-3. (2019).
L. B. Epling*, C. R. Grace*, B. R. Lowe*, J. F. Partridge#, E. J. Enemark#, “Cancer-associated mutants of RNA helicase DDX3X are defective in RNA binding and translation,” JMB 427(9):1779-96 (2015). Featured article, selected for cover illustration.
C. A. Froelich*, S. Kang*, L. B. Epling, S. P. Bell#, E. J. Enemark#, “A conserved MCM single-stranded DNA binding element is essential for replication initiation,” Elife 3: e01993 (2014).
J. M. Miller*, B. T. Arachea*, L. B. Epling, E. J. Enemark, “Analysis of the crystal structure of an active MCM hexamer,” Elife 3: e03433 (2014).
E. J. Enemark and L. Joshua-Tor, “Mechanism of DNA translocation in a replicative hexameric helicase,” Nature 442:270-275 (2006).