Biochemistry and Structural Biology  Back to Main

Faculty Detail    
Campus Address KAUL 552A Zip 0024
Phone  (205) 934-6974
Other websites

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Associate Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Medical Scientist Training Program 

Biographical Sketch 
Igor Chesnokov completed his undergraduate studies and received his Ph.D. degree in Biochemistry at Leningrad State University (Russia) in 1992. He did his post-doctoral work at the University of California in Berkeley and Davis. He joined the department of Biochemistry and Molecular Genetics at UAB in 2002.

Research/Clinical Interest
DNA Replication and Cell Cycle in Eukaryotes
The initiation of DNA replication in higher eukaryotes occurs at thousands of sites along chromosomes. The utilization of such sites in multicellular organisms changes during development and this process is known to affect both gene expression programs and chromosome folding. The Origin Recognition Complex (ORC) is a critical component for DNA replication. In a last few years we have purified and cloned a heteromeric six-subunit ORC from Drosophila cells. ORC binds to DNA at replication origin sites and serves as a scaffold for assembly of other key initiation factors. ORC's functions extend beyond DNA replication. The complex has been implicated in chromosome condensation and the control of M phase events. In particular, we have recently demonstrated that the ORC is critically involved in cytokinesis. We found that the smallest ORC subunit Orc6 is localized to the cell membrane and cleavage furrow of the dividing cells. Our laboratory studies the molecular and biochemical mechanisms of DNA replication and cell cycle progression and the role of ORC in these events. We focus on the following specific projects: 1. determining the mechanism of ORC function in DNA replication. We have developed a Drosophila in vitro replication system, that allows us to investigate the factors required for the ORC-dependent initiation of DNA replication. 2. defining the role of ORC in cytokinesis. The smallest ORC subunit Orc6 interacts with the septin protein Peanut (Pnut) and is involved in cytokinesis in addition to its replication functions. For our studies we use Drosophila as a model system as well as mammalian cell lines. Working with Drosophila will be advantageous for these studies as it allows the use of both biochemical and genetic methods and also permits insights into the developmental as well as tissue specific aspects of replication control. An understanding of the molecular events involved in the initiation of replication and cytokinesis will provide a basis for ultimately controlling these processes. Such control might lead to rationally designed therapies for cancer and may provide the means for regenerating cells lost due to aging, disease or injury.

Selected Publications 
Publication PUBMEDID
Chesnokov I. & Schmid C.W. (1996) Flanking sequences of an Alu source stimulate transcription in vitro by interacting with sequence-specific transcription factors. J. Mol. Evol., 42, 30-36.
Chesnokov I. & Schmid C.W. (1995). Specific Alu binding protein from human sperm chromatin prevents DNA methylation. J. Biol. Chem., 270, 18539-18542.
Chesnokov, I., Chesnokova O., Botchan M. (2003). A cytokinetic function of Drosophila ORC6 protein resides in a domain distinct from its replication activity. Proc. Natl. Acad. Sci. USA, 100(17), 9150-9155.
Chesnokov, I. N. (2007). Multiple functions of the origin recognition complex. Int. Rev. Cytol. 256, 69-109.
Balasov, M., Huijbregts, R. and Chesnokov, I. (2007). The role of Orc6 protein in ORC-dependent DNA binding and replication in Drosophila. Mol. Cell. Biol., 27(8), 3143-3153.
Huijbregts RP, Svitin A, Stinnett MW, Renfrow MB, Chesnokov I. (2009). Drosophila Orc6 facilitates GTPase activity and filament formation of the septin complex. Mol Biol Cell. Jan;20(1):270-81.
Balasov M, Huijbregts RP, Chesnokov I. (2009). Functional analysis of an Orc6 mutant in Drosophila. Proc Natl Acad Sci USA. Jun 30;106(26):10672-7.
Svitin A, Chesnokov I. (2010) Study of DNA replication in Drosophila using cell free in vitro system. Cell Cycle. Feb 15;9(4):815-9.
Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y. (2011) Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB. Proc Natl Acad Sci U S A. 108(18):7373-8.
Chesnokov, I., Remus, D. & Botchan, M. (2001). Functional analysis of wild type and mutant origin recognition complex. Proc. Natl. Acad. Sci. USA, 98, no.21, 11997-12002.
Chesnokov I., Gossen M., Remus D. & Botchan M. (1999). Assembly of functionally active drosophila origin recognition complex from recombinant proteins. Genes and Development, 13, 1289-1296.
Pak D.T., Pflumm M., Chesnokov I., Huang D.W., Kellum R., Marr J., Romanowski P. & Botchan M. (1997). Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes. Cell, 91, 311-323.
Chesnokov I., Chu W.M., Botchan M.R.& Schmid C.W. (1996). p53 inhibits RNA polymerase III directed transcription in promoter dependent manner. Mol. Cell. Biol., 16, 7084-7088.

DNA replication, cytokinesis, Origin Recognition Complex