A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity

Giosalba Burgio, Davide Corona, Gianluca Cestra, Loredana Capobianco, Antonio Musio, Chiara Carrisi, Patrizia Morciano, Giovanni Cenci, Giuseppe E. De Benedetto, Linda Mannini

Risultato della ricerca: Article

31 Citazioni (Scopus)

Abstract

Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and induces an ATR-dependent cell cycle arrest associated with a dramatic reduction of global histone acetylation. Notably, loss of SLC25A1 in short interfering RNA (siRNA)-treated human primary fibroblasts also leads to chromosome breaks and histone acetylation defects, suggesting an evolutionary conserved role for Sea/SLC25A1 in the regulation of chromosome integrity. This study therefore provides an intriguing and unexpected link between intermediary metabolism and epigenetic control of genome stability.
Lingua originaleEnglish
pagine (da-a)4180-4188
Numero di pagine9
RivistaHuman Molecular Genetics
Volume18
Stato di pubblicazionePublished - 2009

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Acetylation
Oceans and Seas
Histones
Chromosomes
Maintenance
Chromosome Breakage
Genomic Instability
Gene Silencing
Cell Cycle Checkpoints
Citric Acid
DNA Repair
Cytosol
Lysine
Drosophila
Chromatin
Cell Cycle
Mitochondria
Fibroblasts
Gene Expression
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics(clinical)
  • Genetics

Cita questo

A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity. / Burgio, Giosalba; Corona, Davide; Cestra, Gianluca; Capobianco, Loredana; Musio, Antonio; Carrisi, Chiara; Morciano, Patrizia; Cenci, Giovanni; De Benedetto, Giuseppe E.; Mannini, Linda.

In: Human Molecular Genetics, Vol. 18, 2009, pag. 4180-4188.

Risultato della ricerca: Article

Burgio, G, Corona, D, Cestra, G, Capobianco, L, Musio, A, Carrisi, C, Morciano, P, Cenci, G, De Benedetto, GE & Mannini, L 2009, 'A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity', Human Molecular Genetics, vol. 18, pagg. 4180-4188.
Burgio, Giosalba ; Corona, Davide ; Cestra, Gianluca ; Capobianco, Loredana ; Musio, Antonio ; Carrisi, Chiara ; Morciano, Patrizia ; Cenci, Giovanni ; De Benedetto, Giuseppe E. ; Mannini, Linda. / A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity. In: Human Molecular Genetics. 2009 ; Vol. 18. pagg. 4180-4188.
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T1 - A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity

AU - Burgio, Giosalba

AU - Corona, Davide

AU - Cestra, Gianluca

AU - Capobianco, Loredana

AU - Musio, Antonio

AU - Carrisi, Chiara

AU - Morciano, Patrizia

AU - Cenci, Giovanni

AU - De Benedetto, Giuseppe E.

AU - Mannini, Linda

PY - 2009

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N2 - Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and induces an ATR-dependent cell cycle arrest associated with a dramatic reduction of global histone acetylation. Notably, loss of SLC25A1 in short interfering RNA (siRNA)-treated human primary fibroblasts also leads to chromosome breaks and histone acetylation defects, suggesting an evolutionary conserved role for Sea/SLC25A1 in the regulation of chromosome integrity. This study therefore provides an intriguing and unexpected link between intermediary metabolism and epigenetic control of genome stability.

AB - Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and induces an ATR-dependent cell cycle arrest associated with a dramatic reduction of global histone acetylation. Notably, loss of SLC25A1 in short interfering RNA (siRNA)-treated human primary fibroblasts also leads to chromosome breaks and histone acetylation defects, suggesting an evolutionary conserved role for Sea/SLC25A1 in the regulation of chromosome integrity. This study therefore provides an intriguing and unexpected link between intermediary metabolism and epigenetic control of genome stability.

KW - citrate, chromosome

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