The Other Genomes: DNA Damage and Repair in Organelles pp. 1-40
Authors: (Pierre Boesch, Frédérique Weber-Lotfi, Noha Ibrahim, Vladislav Tarasenko, Anne Cosset, François Paulus, Robert N. Lightowlers, André Dietrich, Mitochondrial Research Group, Institute for Ageing and Health, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom, and others)
Abstract: DNA in living cells is constantly prone to damage due to both endogenous processes and exogenous deleterious physical and chemical agents. Unrepaired damage can affect gene expression and induce mutations, which in turn may lead to cell dysfunction. Genome integrity is thus maintained through an elaborate set of DNA repair pathways matching the different types of lesions encountered. Specially threatened are the extra-nuclear genomes retained in mitochondria and chloroplasts, as electrons escape from both the respiration and photosynthesis transport chains and give rise to reactive oxygen species. Mitochondrial DNA lesions and mutations are the cause for a variety of severe, incurable human diseases and are associated with aging. Contrary to an initial restrictive view, organelles do not rely on their polyploidy to maintain their genomes, they possess their own regular pathways to repair DNA damage. The present Chapter will focus on these mechanisms, together with the different types of lesions encountered in organelle DNA. All major repair pathways known in the nucleus, with the notable exception of nucleotide excision repair, are likely to operate in mitochondria, with differences depending on the organism considered. Similar pathways have also been documented to various extents in chloroplasts, although in that case information is still missing on mismatch repair. Organelle genomes do not encode DNA repair enzymes but nuclear-encoded gene products are imported from the cytosol and are often shared with the repair systems in the nucleus. On the other hand, mitochondrial and chloroplastic pathways can have their own peculiarities. Organelles might also possess some tolerance mechanisms for lesions which escape repair. The DNA in mitochondria and chloroplasts is packed into membrane-anchored nucleoprotein particles and specific repair appears to occur in association with these nucleoids. Finally, changes in mitochondrial repair are likely to be involved in DNA damage accumulation and age-related decline.