Ph.D. Program in Cellular, Molecular and Industrial Biology

(Project n. 2: Functional Biology of Cellular and Molecular Systems)

Regulation of gene activity and chromatin structure by DNA topoisomerases

The research activity of the group focuses on the functions and structures of DNA topoisomerases. In particular, we aim at establishing the molecular functions of DNA topoisomerases in relation to fundamental cellular processes such as the regulation of transcription and chromatin structures. The aims are pursued with modern post-genomic methodologies such as Chromatin-ImmunoPrecipitation (ChIP), microarrays, and “ChIP on Chip”.
Moreover, we recently developed hybrid Gal4-Topoisomerase I proteins that can specifically relax supercoiled Gal4 motif-containing plasmids and act in-cis in a purified system. In addition, the hybrid enzyme show some specific cellular phenotypes indicating that it may be directed to selected genomic loci in living cells. Thus, such enzyme hybrid proteins can be useful to further dissect Topoisomerase I functions.

the functions and structures of DNA topoisomerases

Selected Publications

- Khobta A, Carlo-Stella C, Capranico G (2004). Specific histone patterns and acetylase/deacetylase activity at the breakpoint-cluster region of the human MLL gene. Cancer Research, 64, 2656-2662.

- Alessandri M, Beretta GL, Ferretti E, Mancia A, Khobta A, Capranico G (2004) Enhanced CPT sensitivity of yeast cells and selective relaxation of Gal4 motif-containing DNA by novel Gal4-Topoisomerase I fusion proteins. Journal of Molecular Biology, 337, 295-305. ASAP article DOI: 10.1016/j.jmb.2004.01.032

- Moro S, Beretta GL, Del Ben D, Nitiss J, Palumbo M, and Capranico G. (2004). Interaction model for anthracycline activity against DNA topoisomerase II. Biochemistry, in press. ASAP article DOI: 10.1021/bi0361665

- Scaldaferro S., Tinelli S., Borgnetto M.E., Azzini A., and Capranico G. (2001) Directed Evolution to Increase Camptothecin Sensitivity of Human DNA Topoisomerase I. Chemistry & Biology, 8, 871-881.

Binaschi M., Borgnetto ME, and Capranico G. (2000). Loss of drug-stimulated topoisomerase II DNA breaks in living cells is different at two unrelated loci. Nucleic Acids Research: 28: 3289-3293.

Beretta GL., Binaschi M., Zagni E., Capuani L., and Capranico G. (1999). Tethering a type IB topoisomerase to a DNA site by enzyme fusion to a heterologous site-selective DNA-binding protein domain. Cancer Research: 59: 3689-3697.

Borgnetto M.E., Zunino F., Tinelli S., Käs E., and Capranico G. (1996). Drug-specific sites of topoisomerase II DNA cleavage in Drosophila chromatin. Heterogeneous localization and reversibility. Cancer Research: 56, 1855-1862.

Research Group

Giovanni Capranico (PhD, group leader)
e-mail: giovanni.capranico@unibo.it

Andriy Khobta (research assistant)

Luca Lotito (post-doctoral fellow)

Francesca Ferri (pre-doctoral fellow)

Alessandra Russo (pre-doctoral fellow)

Location

Laboratory of Molecular Biology
“G. Moruzzi” Department of Biochemistry
via S. Giacomo 11, 40126 Bologna
Tel: +39 051 2094282 / +39 051 2094284
Fax: +39 051 2094283.

lab site: http://www.biotecnologie.unibo.it/capranicolab/index.php