Jon M. Kaguni
Professor
- B.S. 1974, University of Notre Dame
- Ph.D. 1980, University of California, Los Angeles
- NIH Predoctoral Fellow, 1974-79, University of California, Los Angeles
- Damon Runyon-Walter Winchell Research Fellow, 1980-82, Stanford University School of Medicine
- MSU Teacher-Scholar Award, 1991
322 Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-353-6721
Lab: 517-432-3153
FAX: 517-353-9334
Publication search:
Jon M. Kaguni
Research Interests
Chromosomal replication in all organisms is an event that
is tightly coupled to cell growth. This process can be separated into
stages of initiation of DNA replication, progression of replication forks,
termination of chromosomal DNA synthesis and segregation of daughter
chromosomes into respective cells. Studies indicate that regulation of DNA
replication occurs during the initiation of a cycle of chromosomal
replication.
Of over 20 different genes that are required for
replication of the Escherichia coli chromosome, the dnaA gene is
uniquely required to initiate this process. My laboratory has focussed on
the role of the dnaA gene product with the long range objectives of
understanding biochemically the initiation of chromosomal replication, and
its regulation. This protein is a sequence-specific DNA binding protein
that binds to sites in the chromosomal origin of E. coli and in
promoter regions of genes it regulates. One major approach has been to
study the biochemical functions of DnaA protein in the step of initiation
of DNA replication. The second is to isolate and characterize novel mutant
forms of DnaA protein defective in replication. The third is to correlate
structural domains of DnaA protein to its various functions.
From these
approaches, we recently characterized a collection of dnaA mutants by
genetic and biochemical methods that identify four functional domains. One
domain near the N-terminus appears to be involved in interaction with DnaB
protein, the replicative helicase responsible for progressive replication
fork movement. MORE
Recent Publications
Chodavarapu S, Gomez R, Vicente M, Kaguni JM. (2008) Escherichia coli Dps interacts with DnaA protein to impede initiation: a model of adaptive mutation. Mol Microbiol. Feb 15; [Epub ahead of print]
Chodavarapu S, Felczak MM, Yaniv JR, Kaguni JM. (2008) Escherichia coli DnaA interacts with HU in initiation at the E. coli replication origin. Mol Microbiol. 67(4):781-92.
Hupert-Kocurek K, Sage JM, Makowska-Grzyska M, Kaguni JM. (2007) A Genetic Method to Analyze Essential Genes of Escherichia coli. Appl Environ Microbiol. 73(21):7075-82.
Kaguni JM. (2006) DnaA: Controlling the initiation of bacterial DNA replication and more. Annu Rev Microbiol. 60:351-375.
Walker JR, Severson KA, Hermandson MJ, Blinkova A, Carr KM, Kaguni JM. (2006)
Escherichia coli DnaA protein: specific biochemical defects of mutant DnaAs
reduce initiation frequency to suppress a temperature-sensitive dnaX mutation.
Biochimie. 88(1):1-10. Epub 2005 Sep 21.
Felczak MM, Simmons LA, Kaguni JM.
(2005) An essential tryptophan of Escherichia coli DnaA protein functions in
oligomerization at the E. coli replication origin.
J Biol Chem. 280(26):24627-33. Epub 2005 May 5.
Felczak MM, Kaguni JM. (2004)
The box VII motif of Escherichia coli DnaA protein is required for DnaA oligomerization at the E. coli replication origin.
J Biol Chem. 279(49):51156-62. Epub Sep 14, 2004.
Simmons LA, Breier AM, Cozzarelli NR, Kaguni JM. (2004)
Hyperinitiation of DNA replication in Escherichia coli leads to replication fork collapse and inviability. Mol Microbiol. 51(2):349-58.
Simmons LA, Felczak M, Kaguni JM. (2003)
DnaA Protein of Escherichia coli: oligomerization at the E. coli chromosomal origin is required for initiation and involves specific N-terminal amino acids.
Mol Microbiol. 49(3):849-58.
Simmons, Lyle A., and Kaguni, Jon M. (2003) The dnaAcos allele of E. coli:
hyperactive initiation is due to substitution of A184V and Y271H, resulting
in defective ATP binding and aberrant DNA replication control. Mol. Micro. 47(3):755-65. MORE