Mammalian Mitochondrial DNA Replication
The necessity for DNA repair in mitochondria was recognized over 50 years ago when the free radical theory was proposed by Harman. It was hypothesized that the aging process is due to the cumulative build up of oxidative damage in mitochondrial DNA (mtDNA). Since then, a great deal of evidence has been found in support of this hypothesis. Additionally, links have been found between damaged mtDNA and diseases such as Leber’s hereditary optic neuropathy, chronic progressive external opthalmoplegia, Alzheimer’s, Parkinson’s, and cancer. The most extensively studied mitochondrial DNA repair mechanism is base excision repair. Mitochondria from several organisms contain DNA repair enzymes such as glycosylase, AP endonuclease and DNA ligase III. The mechanisms for double-strand break (DSB) repair are much less characterized. DSBs are arguably the most drastic type of DNA damage and are repaired through recombination or non-homologous end joining. Analysis of mtDNA rearrangements has indicated that homologous recombination occurs in mitochondria from fungi, plants, and animals. However, the proteins and enzymes that carry out this process have not been isolated.
Bacteriophage T4 Recombination-dependent DNA Repair
T4 phage is able to perform all the functions required for the replication and maintenance of its genome. Decades of research has proven T4 phage to be an excellent model system. The molecular mechanisms of the core DNA replication proteins (e.g., polymerase, helicase, clamp protein) are well conserved from phage to humans. It is expected that this conservation will extend to the DNA repair enzymes.