DNA double-strand break repair proteins in mitochondria of mammalian cells

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DNA double-strand break (DSB) is the most dangerous DNA damage. One DNA DSB can be sufficient to kill a cell, if it is not repaired. DNA DSB can be induced both exogenously, e.g., by ionizing radiation (IR), chemicals, and chemotherapeutics, and endogenously, e.g., in the process of recombination and replication or due to oxidative stresses. Two major pathways exist in mammalian cells for the repair of DNA DSB : nonhomologous DNA-end-joining (NHEJ) repair and homologous recombination (HR). The NHEJ repair process requires Ku70, Ku80, XRCC4, DNA Ligase IV, and DNA-PKcs. The HR repair process requires Rad51 and Rad52. The NHEJ repair process, which is responsible for repairing a major fraction of DNA DSB in somatic cells of all multicellular eukaryotes, is thought to begin with the binding of Ku. The mechanism of Ku-end recognition has been suggested by the recent resolution of the crystal structure of Ku: ring-like structure with high affinity DNA binding site around the central pore. Evidence for the importance of Ku in the NHEJ repair process has been reported. Cells genetically deficient in Ku are sensitive to ionizing radiation and other agents (e.g. etoposide) that generate DNA DSB. Mammals possess two cellular genomes, one in the nucleus and the other in the mitochondria. It is not well known whether in contrast to the nucleus, mammalian mitochondria are able to repair DSB, although it was reported that Ku80 is localized in mammalian mitochondria and functions in a DNA-end binding activity. In this study, I could not detect DSB-repair proteins, i.e., Ku70, Ku80, XRCC4 and Rad52 in mammal' s mitochondria examined.