Maki Asano

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Assistant Professor

Tumor Microenvironment Program,
        The Comprehensive Cancer Center
Department of Molecular and Cellular Biochemistry,
        College of Medicine
Department of Molecular Genetics,
        College of Biological Sciences
The Ohio State University


812 Biomedical Research Tower (BRT)
460 West 12th Avenue
Columbus OH 43210
Phone: 614-688-4164
Fax: 614-688-4181
E-mail address: maki.asano@osumc.edu 

M.D. - Tohoku University, Japan
Ph.D. - Kyoto University, Japan
Post Doctoral - Duke University

Our laboratory studies DNA replication initiation factors and the roles they play to regulate different modes of DNA replication during organism development.

We employ molecular, biochemical and genetic approaches in our research. We use Drosophila as a model system for the following reasons:

1) Most of the components involved in DNA replication regulation are remarkably conserved in flies and mammals and therefore our findings will be directly applicable to mammals.
2) During Drosophila development, a number of tissues and cell types offer excellent opportunities to study cell cycle progression in unperturbed cells of the intact animal.
3) An unparalleled combination of genetic and molecular tools is available for use in Drosophila. Prominent among these are the ability to easily prepare transgenic animals or mutants by gene-targeting, highly developed technology for tissue- and cell type-specific mis-expression in vivo, and a complete and well annotated genomic sequence.

Our current research projects are:
1) Molecular mechanisms of endoreplication initiation: we have discovered that motitic DNA replication and endoreplication use different pre-Replication Complex (pre-RC) components (Park & Asano, 2008). We will identify pre-RC components specific to endoreplication using genetic (ex. Production of cdc6 mutants) and biochemical (ex. Purification of Cdc6 and Cdt1/Dup interacting proteins) approaches.
2) Molecular mechanisms of ORC1 function outside of DNA replication: Although the ORC has a primary role in directing the initiation of DNA replication, we and others have suggested that it plays an important role in other aspects of the cell cycle such as chromosome condensation, chromosome segregation, and cytokinesis as well as non-cell cycle events such as heterochromatin-associated transcriptional silencing and control of synaptic plasticity. We will identify and characterize new ORC1-interacting factors, i.e. its functional partner in each function.
3) Identification of new targets of Anaphase Promoting Complex (APC): We have identified a novel APC motif, the “ORC1-destruction box” (O-box), which mediates ORC1 degradation by APC (Araki et al., 2005). Using combination of purified ubiquitination assays in vitro and protein degradation assay in vivo in cell culture and transgenic flies we will identify new O-box proteins and their involvement in cell cycle control.

Recent Publications:

• Asano M (2009) "Endoreplication: The advantage to initiating DNA replication without the ORC?" Fly (Austin) Apr-Jun;3(2):173-5.
• Park SY and Asano M (2008) "The origin recognition complex is dispensable for endoreplication in Drosophila" Proc Natl Acad Sci USA 105(34):12343-8.
• Narbonne-Reveau K, Senger S, Pal M, Herr A, Richardson HE, Asano M, Deak P and Lilly MA (2008) "APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle" Development 135(8):1451-61. 
• Wu Q, Guo Y, Yamada A, Perry JA, Wang MZ, Araki M, Freel CD, Tung JJ, Tang W, Margolis SS, Jackson PK, Yamano H, Asano M and Kornbluth S (2007) "A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest" Curr Biol 7(3):213-24.
• Okudaira K, Ohno K, Yoshida H, Asano M, Hirose F and Yamaguchi M (2005) "Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway" Biochim Biophys Acta 1732(1-3):23-30.
• Araki M, Yu H and Asano M (2005) "A novel motif governs APC-dependent degradation of Drosophila ORC1 in vivo" Genes Dev 19(20):2458-65. 
• Araki M, Wharton RP, Tang Z, Yu H and Asano M (1999) "Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila" EMBO J 22(22):6115-26.
• Asano M and Wharton RP (1999) "E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila" EMBO J 18(9):2435-48.
• Asano M, Nevins JR and Wharton RP (1996) "Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs" Genes Dev 10(11):1422-32.
• Ito K, Asano M, Hughes P, Kohzaki H, Masutani C, Hanaoka F, Kerppola T, Curran T, Murakami Y and Ito Y (1996) "c-Jun stimulates origin-dependent DNA unwinding by polyomavirus large Tantigen" EMBO J 15(20):5636-46.
• Ishikawa H, Asano M, Kanda T, Kumar S, Gélinas C and Ito Y (1993) "Two novel functions associated with the Rel oncoproteins: DNA replication and cell-specific transcriptional activation" Oncogene 8(11):2889-96.
• Asano M, Ishikawa H and Ito Y (1992) "Possible involvement of nuclear oncoproteins in regulation of DNA replication" Tohoku J Exp Med 168(2):183-7. Review.
• Asano M, Murakami Y, Furukawa K, Yamaguchi-Iwai Y, Satake M and Ito Y 1990) "A polyomavirus enhancer-binding protein, PEBP5, responsive to 12-O-tetradecanoylphorbol-13-acetate but distinct from AP-1" J Virol 64(12):5927-38.
• Kamachi Y, Ogawa E, Asano M, Ishida S, Murakami Y, Satake M, Ito Y and Shigesada K (1990) "Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer" J Virol 64(10):4808-19.
• Murakami Y, Asano M, Satake M and Ito Y (1990) "A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer" Oncogene 5(1):5-13.