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Mitochondrial, but not Nuclear Ligase3 is Required for Cellular Viability

Bennett Van Houten, Ph.D.
University of Pittsburgh
NIEHS Grant R01ES19566

A multi-institutional team of scientists including former NIEHS Principal Investigator, Ben Van Houten, has determined that mitochondrial DNA ligase3 (Lig3), an enzyme involved in various DNA repair pathways, is necessary for cellular growth and viability as compared to the nuclear version of the enzyme. These findings were made through a series of exquisite experiments which incorporated various forms of the gene coding for Lig3 in mouse embryonic stem cells.

Previous research has demonstrated the importance of the nuclear complex of Lig3 and its partner protein Xrcc-1 in DNA single-strand break repair. The full characterization of Lig3 has been hampered by the fact that deletion of its gene is embryonically lethal in mice. In the current studies, the investigators introduced various forms of Lig3 into mouse embryonic stem cells containing a conditional allele for Lig3 that could be deleted with Cre recombinase. This approach enabled them to determine that mitochondrial Lig3, but not nuclear, is necessary for cell viability. They also found that substitution of Lig1for Lig3in the mitochondria maintains cellular viability.

Citation: Simsek D, Furda A, Gao Y, Artus J, Brunet E, Hadjantonakis AK, Van Houten B, Shuman S, McKinnon PJ, Jasin M. Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. Nature. 2011 Mar 10;471(7337):245-8.

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