Drug-induced genome instability: translation from yeast to human

Programme / Research groups

This AIMMS-PhD project 10-001-204 is part of the programmes Molecular mechanisms of biological processes and Biomarkers and diagnostics

The project bridges the two research groups Molecular Toxicology (FEW, PI: Chris Vos) and Genetics (FALW, PI: Jan Kooter).

Keywords

yeast, drugs, tumor-suppression, aneuploidy

Summary

It is crucial for an organism to keep the number and integrity of chromosomes intact since several diseases are the result of genomic instability. Many tumors, for example, are characterized by DNA rearrangements and changes in gene copy numbers. The causes of genome instability are not always known, but in part it is due to an interplay between genetic mutations and factors to which cells are exposed to, including particular drugs. We have identified in baker’s yeast, a relatively simple research model organism, several genes which protect cells from drug-induced genome alterations. Some of these genes are also present in human. In order to understand the role of the proteins encoded by these genes in preventing genome alterations and how drugs may interfere with this process, we will study their properties in yeast and human. In human, expression of these genes will be examined in normal and cancer cells in the presence and absence of various drugs used in the clinic with the aim to examine their potential use as translational biomarkers for diagnostic and therapeutic purposes. (Read more)