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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Mitochondrial effects of the pleiotropic proteasomal mutation mpr1/rpn11: uncoupling from cell cycle defects in
T Rinaldi1, R Ricordy, M Bolotin-Fukuhara
1Department of Cell and Developmental Biology, Pasteur Institute Cenci Bolognetti Foundation, University of Rome I, Piazzale Aldo Moro 5, 00185 Rome, Italy. teresa.rinaldi@uniroma1.it
Abstract:
We have previously characterized a Saccharomyces cerevisiae mutant which contains a mutation in the essential rpn11/mpr1 gene coding for the proteasomal regulatory subunit Rpn11. The mpr1-1 mutation shows the phenotypic characteristics generally associated with proteasomal mutations, such as cell cycle defects and accumulation of polyubiquitinated proteins. However, for the first time, mitochondrial defects have also been found to be a consequence of a mutation in a proteasomal gene (Mol. Biol. Cell 9 (1998) 2917-2931). Since the mutant strain is thermosensitive both on glucose and on glycerol, we searched for revertants in order to shed light on the Rpn11/Mpr1 functions. Spontaneous revertants able to grow on glucose but not on glycerol at 36 degrees C were isolated, and, only from them, revertants able to grow at 36 degrees C on glycerol were selected. Revertants of the two classes were found to be extragenic. The detailed characterization of these extragenic suppressors demonstrates that the phenotypes related to cell cycle defects can be dissociated from those concerned with mitochondrial organization.
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