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Title:
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Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability
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Author:
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Díaz de la Loza, María del Carmen; Gallardo, Mercedes; García-Rubio, María Luisa; Izquierdo, Alicia; Herrero Perpiñán, Enrique; Aguilera, Andrés; Wellinger, Ralf Erik
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Notes:
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Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron–sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron–sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron–sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.
European Union (EUROFAN II to A.A.); Spanish Ministry of Science and Innovation (BIO2003-07172 and BIO2006-08051 to R.E.W. and Consolider Ingenio 2010, CSD2007-0015); Junta de Andalucía (P08-CTS-04297 to R.E.W.); Pre-doctoral FPI fellowship from the Spanish Ministry of Science and Innovation (to M.D.L.). Funding for open access charge: Proyecto de investigación de excelencia (P08-CTS-04297) of the Junta de Andalucía. |
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Subject(s):
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-Iron-Sulfur Proteins
-Mitochondrial proteins
-Saccharomyces cerevisiae proteins
-Zim 17 protein
-Llevat de cervesa
-Expressió gènica
-Ferro |
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Rights:
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cc-by-nc, (c) Díaz de la Loza et al., 2011
http://creativecommons.org/licenses/by-nc/2.5/es/deed.ca
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Document type:
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article
publishedVersion |
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Published by:
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Oxford University Press
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Share:
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