Universitą degli studi di Pavia


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Giulotto research activity

Genome instability in carcinogenesis and evolution: telomeres, centromeres and mobile elements

The research projects concern the molecular mechanisms involved in the maintenance of mammalian genome integrity, which play a crucial role both in carcinogenesis and in evolution. To this purpose bio-molecular, cytogenetic and bio-informatic methods are used.
Chromosome ends, the so called telomeres, are essential for genome stability. Telomere misfunction causes chromosome rearrangements and can lead to cancer in somatic cells, while it may represent an evolutionary force when occurring in the germ line. The purpose of our research is to identify factors involved in telomere metabolism with particular emphasis on the non-coding RNA molecules transcribed by telomeres.
Besides telomeres, the functional elements required to maintain chromosome integrity are the centromeres which drive chromosome separation during cell division. The repositioning of centromeres is an important mechanism of genome evolution; morevoer, alterations in chromosome segregation contribute to carcinogenesis and tumour progression. Centromeric DNA is characterised by the presence of tandem repeats of short sequences named satellite DNA. We have discovered that, in the genus Equus (horses, asses and zebras), several centromeres are devoid of satellite DNA because they are evolutionarily recent. The simple sequence organization of these centromeres makes them an ideal model system for the analysis of centromere function at the molecular level.
Several DNA sequences sharing the ability to be inserted into genomes can cause genome rearrangements. Using a comparative genomic approach we study the mechanisms of insertion of some of these sequences: interstitial telomeres, DNA sequences of mitochondrial origin and transposable elements. These insertion elements are also used as markers for the construction of evolutionary trees and for the analysis of genetic variability.
Finally, taking advantage of our knowledge on gene amplification and in collaboration with biotec companies, we construct cell lines over-expressing pharmaceutically relevant proteins.

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