Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair

Deniz Simsek, Amy Furda, Yankun Gao, Jérôme Artus, Erika Brunet, Anna-Katerina Hadjantonakis, Bennett Van Houten, Stewart Shuman, Peter J. McKinnon and Maria Jasin ()
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Deniz Simsek: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center
Amy Furda: University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Hillman Cancer Center
Yankun Gao: St Jude Children’s Research Hospital
Jérôme Artus: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center
Erika Brunet: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center
Anna-Katerina Hadjantonakis: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center
Bennett Van Houten: University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Hillman Cancer Center
Stewart Shuman: Weill Cornell Graduate School of Medical Sciences
Peter J. McKinnon: St Jude Children’s Research Hospital
Maria Jasin: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center

Nature, 2011, vol. 471, issue 7337, 245-248

Abstract: A mitochondrial role for DNA ligase III Mammalian cells contain three different DNA ligase enzymes, each with different properties but all involved in DNA replication and repair. Ligase III (Lig3) is known to form a complex with the nuclear DNA repair protein Xrcc1, and Lig3 null animals cannot be made. This raises the question of whether this nuclear role in base-excision repair (BER) is the critical function of Lig3 that maintains viability. Two groups reporting in this issue of Nature investigate different aspects of Lig3 function in vivo, both concluding that the catalytic activity of Lig3 is critical for mitochondrial DNA maintenance and viability, but unexpectedly, is dispensable for Xrcc1-mediated nuclear BER. These findings suggest that Lig3 mutations might cause some of the human syndromes associated with defects in the replication and/or repair of mitochondrial DNA.

Date: 2011
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DOI: 10.1038/nature09794

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