Our focus is on eukaryotic DNA replication and its control, with emphasis on the identification of the protein components involved in these processes. The human replicative helicase, consisting of Cc45-Mcm2-7-GINS (CMG) and the replicative DNA polymerases, catalyze leading and lagging strand syntheses. Our goal is to recapitulate in vitro the in vivo observations suggesting that Pol ε catalyzes leading strand DNA synthesis while Pol δ plus Pol α-primase complex support lagging strand synthesis. We utilize a primed 200-nt circle containing only three nucleotides so leading strands can be measured conveniently using dATP incorporation while lagging strand can be followed by dTTP incorporation. We suggest that the CMG complex is the protein core at the replication fork. Proteins involved in replication, including DNA polymerases, Ctf4, FACT, Tim-Tipin, etc., interact with the CMG complex and constitute the moving replisome. We are investigating these interactions and their influence on the CMG helicase activity both in vitro and in vivo. Alterations in components of the CMG complex play important roles in DNA replication. Specific human mutations in Psf1 (a GINS component) have been detected and their effects on the formation of GINS and CMG are being investigated. A number of these mutations lead to developmental defects; we plan to determine whether alterations in DNA replication in cells isolated from the Psf1 human mutants contribute to the observed phenotypic defects.
Jerard Hurwitz, PhD
Research FocusMolecular biologist Jerard Hurwitz focuses on mechanisms of eukaryotic DNA replication and the isolation and characterization of the proteins involved.
- PhD, Western Reserve University
- Li Z, Huang RY, Yopp DC, Hileman TH, Santangelo TJ, Hurwitz J, Hudgens JW, Kelman Z. A novel mechanism for regulating the activity of proliferating cell nuclear antigen by a small protein. Nucleic Acids Res. 2014;42(9):5776-89. doi: 10.1093/nar/gku239. Epub 2014 Apr 11. [PMID: 24728986].
- Kang YH, Farina A, Bermudez VP, Tappin I, Du F, Galal WC, Hurwitz J. Interaction between human Ctf4 and the Cdc45/Mcm2-7/GINS (CMG) replicative helicase. Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19760-5. doi: 10.1073/pnas.1320202110. Epub 2013 Nov 19. [PMID:24255107].
- Pfizer Science Award, History of Science Society (1984-1989)
- Louis and Bert Freeman Foundation Prize for Research, New York Academy of Science (1982)
- Fogarty Scholar Award, Fogarty International Center (1980)
- Member, National Academy of Sciences (1974)
- Fellow, John SimonGuggenheim Memorial Foundation (1968)
- Professorship, American Cancer Society (1963-1998)
- Eli Lilly Award in Biochemistry, American Chemistry Society (1962)
- Sigma Xi Award (1962)