The Laboratory of Yeast Molecular Genetics of the ICGEB-Trieste has identified two genes, controlling chromosomal translocations, which are related to some type of human tumors such as leukemia. The research, published on the Journal Plos One, used as a model the microorganism Saccharomyces cerevisiae, which is the common yeast for baking and brewing. S. cerevisiae belongs to the Fungi kingdom and it divides by budding.

This yeast has been the first microorganism entirely sequenced and it is the most important model in the molecular studies of eukaryotic cells. For the biotechnologists, S. cerevisiae is an essential instrument to find out the function of the molecular mechanisms of those genes that are homologues to our Homo sapiens ones. Moreover, the same Yeast Molecular genetics Laboratory, headed by Prof. Carlo Bruschi, participated to the international project of the Yeast Genome Sequencing and it organized the public data release during a memorable conference held in Trieste in 1996 with the presence of the father of the DNA, the Nobel Prize Winner James Watson.

Applying to yeast cells a molecular system, developed in Bruschi's lab, named BIT (Bridge-Induced Translocation), capable of triggering chromosomal translocation between heterologous chromosomes, the researchers identified the genes RAD54 and RDH54 (homologues of the human RAD54A and RAD54B), which are able to promote or prevent the chromosomal translocation.

In effect, the chromosomal translocations characterize many types of malignant neoplastic diseases and their detection may help in the diagnosis of solid and liquid tumors. Although the molecular players responsible for the gross chromosomal rearrangements are still under elucidation, it is well known the correlation between the presence of these genetic aberrations and the tumor formation. The molecular mechanism leading to translocations is so far only partially described, but until now, it was not clear whether a translocation is the cause of a tumor or, vice-versa, it is a consequence of it.

The discovery of the researchers from Trieste sheds light on these two genes as important actors in the process to generate the mutations triggering the tumor formation. Their role is explained by Valentina Tosato, Communicating Author of the research: "We demonstrated the mechanism with which RAD54 promotes the chromosomal translocations; its over-expression is present in many types of tumors (such as the prostatic tumor) that are characterized by a high number of gross chromosomal rearrangements. On the contrary, RDH54 allows the cell to maintain the translocated chromosome and to transmit it to the daughter cells. Moreover, it has an important role in translocations between homologous chromosomes and it modulates the possible loss of heterozygosity for recessive oncogenes and therefore the possible neoplastic formation".

Thanks to the BIT technology, the Yeast Molecular Genetics Group has been the first to induce a targeted chromosomal translocation at specific loci of the genome of an eukaryotic wild type cell (yeast) scrambling randomly a great number of genes and allowing therefore to re-program the cell for ad hoc cellular functions. Furthermore, this project might open the doors in the future to new protocols of chromosomal therapy as substitute to the standard gene therapy for genetic diseases that so far did not produce the hopeful results.