Ph.D. Program in Cellular, Molecular and Industrial Biology (Project n. 1: Physiology and Cellular Biology)
The centromere is a nucleoproteic complex that acts as an essential cis-active element of eukaryotic chromosomes, by controlling the segregation of sister chromatids during cell division. The centromere of higher eukaryotes consists of repetitive elements, spanning several mega bases of DNA, the base composition and organization of which not only differs from species to species, but even between different chromosomes of the same species. Conversely, the proteinaceous component (kinetochore) is composed of a group of proteins (CENP-A, CENP-B, CENP-C, hmis12 etc). Whether specific DNA sequences are important for the assembly of an active centromere is still an open question. In fact, while some experimental data support epigenetic mechanisms controlling centromere assembly, attempts to create human artificial chromosomes point to the alpha-satellite DNA as the key player in active centromere formation. Neocentromeres are newly formed centromeres generally derived from rearranged chromosome fragments that have separated from the original centromere and represent a gain of centromeric function of a normally euchromatic chromosomal Although they display a primary constriction and are characterized by the same set of centromere proteins found at conventional active centromeres (for example CENP-A and CENP-C), they lack typical DNA repetitive elements found in centromeric heterochromatin. The aims of this our research is the definition of the molecular mechanisms underlying the DNA/protein interactions occurring at an active centromere/kinetochore complex. Specifically three main issues will address: 1) definition and characterization of the DNA sequences involved in the formation of a human neocentromere arisen from different chromosome regions; 2) investigation of a possible species-specific role of CENP-A and CENP-C in the recognition of species-specific centromere DNAs; 3) analysis of the physical interactions between CENP-C and other kinetochore proteins, specifically CENP-A and histone H3 when assembled onto centromeric DNA.
Research Group
Giuliano Della Valle (Full professor)
Stefania Purgato Contrattista Regione Emilia Romagna
Monica Zoli Dottoranda
