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Sims J.,Yeast Molecular Genetics Group | Sims J.,Max Perutz Laboratories | Bruschi C.V.,Yeast Molecular Genetics Group | Bertin C.,University of Rennes 1 | And 7 more authors.
Molecular Genetics and Genomics | Year: 2016

Chromosome translocation is a major genomic event for a cell, affecting almost every of its life aspects ranging from metabolism, organelle maintenance and homeostasis to gene maintenance and expression. By using the bridge-induced translocation system, we defined the effects of induced chromosome translocation on the chronological life span (CLS) of yeast with particular interest to the oxidative stress condition. The results demonstrate that every translocant strain has a different CLS, but all have a high increase in reactive oxygen species and in lipid peroxides levels at the end of the life span. This could be due to the very unique and strong deregulation of the oxidative stress network. Furthermore, the loss of the translocated chromosome occurs at the end of the life span and is locus dependent. Additionally, the RDH54 gene may play a role in the correct segregation of the translocant chromosome, since in its absence there is an increase in loss of the bridge-induced translocated chromosome. © 2015, Springer-Verlag Berlin Heidelberg. Source


Nikitin D.V.,Yeast Molecular Genetics Group | Nikitin D.V.,Russian Academy of Sciences | Bruschi C.V.,Yeast Molecular Genetics Group | Sims J.,Yeast Molecular Genetics Group | And 3 more authors.
European Journal of Cell Biology | Year: 2014

Chromosome translocations are often observed in cancer cells, being in some cases the cause of neoplastic transformation while in others the results of it. In previous works, we reproduced this major genomic rearrangement by bridge-induced chromosome translocation (BIT) technology in the model eukaryote Saccharomyces cerevisiae and reported that it affects DNA replication, cell cycle, karyogamy, and cytokinesis while it produces genetic instability. In the present work, we further discovered that this event can lead to increased resistance to anticancer chemicals like Doxorubicin and Latrunculin A via an endocytic actin network deregulation triggered by over-expression of the PRK1 serine/threonine protein kinase gene. This effect is further enhanced by the overexpression of PDR1 and PDR3 transcriptional regulators of pleiotropic drug resistance factors. However, when the actin depolymerizing drug Latrunculin A is forcefully allowed to penetrate through their altered cell wall and membrane barriers, it can kill translocants more efficiently than wild type cells. These observations provide an example of an acquired anticancer drug resistance mechanism and could serve as a lead to how it might be overcome, as any treatment inhibiting genome rearrangements could increase the positive outcome of anticancer therapy by lowering cellular drug resistance. © 2014 Elsevier GmbH. Source

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