Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

被引：0
作者：
Alice Bourdon
Limor Minai
Valérie Serre
Jean-Philippe Jais
Emmanuelle Sarzi
Sophie Aubert
Dominique Chrétien
Pascale de Lonlay
Véronique Paquis-Flucklinger
Hirofumi Arakawa
Yusuke Nakamura
Arnold Munnich
Agnès Rötig
机构：
[1] Institut national de la santé et de la recherche médicale U781 and Service de Génétique,Department of Medical Genetics
[2] Hôpital Necker-Enfants Malades,undefined
[3] 149 rue de Sèvres,undefined
[4] Université Paris 7,undefined
[5] 2 Place Jussieu,undefined
[6] Service de biostatistique et Informatique Médicale Université René Descartes,undefined
[7] Faculté de Médecine,undefined
[8] Hôpital Necker-Enfants Malades,undefined
[9] 149 rue de Sèvres,undefined
[10] Archet 2 Hospital,undefined
[11] 151 Route St Antoine de Ginestière,undefined
[12] Human Genome Center,undefined
[13] Institute of Medical Science,undefined
[14] University of Tokyo,undefined
[15] 4-6-1 Shirikanedai,undefined
[16] Minato-ku,undefined
来源：
Nature Genetics | 2007年 / 39卷
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摘要：
Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5′-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1–2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b−/− mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis.
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页码：776 / 780
页数：4
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