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Education/Training

B.A. Biology		1978		Oberlin College
Ph.D. Microbiology & Immunology		1984		University of Colorado School of Medicine
Postdoctoral Fellow				Harvard Medical Center

Research Interests

Dr. Nakai's research examines mechanisms involved in linking DNA replication to recombination, an important process for chromosomal replication, recombination, and repair in both prokaryotic and eukaryotic cells. Careful control of these reactions by factors such as tumor suppressor p53 plays a critical role in the maintenance of the cellular genome. Work has been focused on understanding how the protein apparatus that catalyzes recombination is remodeled to form a replisome, the proteins that catalyzes the propagation of a replication fork. A model biochemical system used in the laboratory is the transposition of bacteriophage Mu. During Mu lytic development, the phage-encoded transposition proteins A and B direct the 100 to 200-fold amplification of Mu DNA by host replication proteins. The MuA transposase resembles the retroviral integrases that catalyze the insertion of proviral DNA into the host chromosome. The Mu replication reaction can be catalyzed by 15 purified proteins, two of which are encoded by Mu, and at least one additional host factor that is yet to be identified. The studies have revealed the function of a specialized cellular apparatus for initiating DNA synthesis by recombination, an apparatus specifically recruited by the MuA transposase. Dr. Nakai's group is also examining molecular signals that induce transposition and chromosomal rearrangement. Conformational states of key regulator proteins, including the prionlike dissemination of conformational changes among these molecules, appear to play a critical role in this process.

Recent Publications

View All PubMed articles by Nakai, H (May contain authors with the same name)

North, S. H., and Nakai H. (2005)
Host factors that promote transpososome disassembly and the PriA-PriC pathway for restart primosome assembly
Mol. Microbiol. 56: 1601-1616 Medline

Chen, H. W., North, S. H., and Nakai, H. (2004)
Properties of the PriA helicase domain and its role in binding PriA to specific DNA structures.
J. Biol. Chem. 37: 38503-38512 Medline

Defenbaugh, D., and Nakai, H. (2003)
A Context-Dependent ClpX Recognition Determinant Located at the C Terminus of Phage Mu Repressor
J. Biol. Chem. 278: 52333-52339 Medline

Marshall-Batty, K. R., and Nakai, H. (2003)
Trans-targeting of phage Mu repressor is promoted by conformational changes that expose its ClpX recognition determinant
J. Biol. Chem. 278:1612-1617 Medline

Mukhopadhyay, B., Marshall-Batty, K. R., Kim, B. D., O'Handley, D., and Nakai, H. (2003)
Modulation of phage Mu represor DNA binding and degradation by distinct determinants in its C-terminal domain.
Mol. Microbiol. 47:171-182 Medline

O'Handley, D., and Nakai, H. (2002)
Derepression of bacteriophage Mu transposition functions by truncated forms of the immunity repressor
J. Mol. Biol. 322: 311-324 Medline

Jones, J. M., and Nakai, H. (2001)
Escherichia coli PriA helicase: Fork binding orients the helicase to unwind the lagging strand side of arrested replication forks
J. Mol. Biol. 312: 935-947 Medline

Rai, S. S., O'Handley, D., and Nakai, H. (2001)
Conformational dynamics of a transposition repressor in modulating DNA binding
J. Mol. Biol. 312:311-322 Medline

Jones, J. M., and Nakai, H. (1999)
Duplex opening by primosome protein PriA for replisome assembly on a recombination intermediate
J. Mol. Biol. 289: 503-515 Medline

Jones, J. M., and Nakai, H. (1997)
The phiX174-type primosome promotes replisome assembly at the site of recombination in bacteriophage Mu transposition.
EMBO J. 16:6886-6895 Medline

Last Modified: 1/3/2008 [/FMP-IF]