Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability

Díaz de la Loza, María del Carmen; Gallardo, Mercedes; García-Rubio, María Luisa; Izquierdo, Alicia; Herrero Perpiñán, Enrique; Aguilera, Andrés; Wellinger, Ralf Erik

doi:https://doi.org/10.1093/nar/gkr193

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2011

Author

Díaz de la Loza, María del Carmen

Gallardo, Mercedes

García-Rubio, María Luisa

Izquierdo, Alicia

Herrero Perpiñán, Enrique

Aguilera, Andrés

Wellinger, Ralf Erik

Suggested citation

Díaz de la Loza, María del Carmen; Gallardo, Mercedes; García-Rubio, María Luisa; Izquierdo, Alicia; Herrero Perpiñán, Enrique; Aguilera, Andrés; Wellinger, Ralf Erik; . (2011) . Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability. Nucleic Acids Research, 2011, vol. 39, núm. 14, p. 6002-6015. https://doi.org/10.1093/nar/gkr193.

Abstract

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.

URI

http://hdl.handle.net/10459.1/46367

DOI

https://doi.org/10.1093/nar/gkr193

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Nucleic Acids Research, 2011, vol. 39, núm. 14, p. 6002-6015

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Except where otherwise noted, this item's license is described as cc-by-nc, (c) Díaz de la Loza et al., 2011