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Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication ( POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.<\/jats:p>","DOI":"10.1177\/0883073814537380","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T05:51:35Z","timestamp":1404280295000},"page":"1216-1224","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":52,"title":["Defects of Mitochondrial DNA Replication"],"prefix":"10.1177","volume":"29","author":[{"given":"William C.","family":"Copeland","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,6,30]]},"reference":[{"key":"bibr1-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng060"},{"key":"bibr2-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161455"},{"key":"bibr3-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1021\/cr040463d"},{"key":"bibr4-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.53.38197"},{"key":"bibr5-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600257"},{"key":"bibr6-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.060305.152028"},{"key":"bibr7-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"bibr8-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.59.053006.104646"},{"key":"bibr9-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20824"},{"key":"bibr10-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.105"},{"key":"bibr11-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1038\/90034"},{"key":"bibr12-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.151795"},{"key":"bibr13-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5565-9"},{"key":"bibr14-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.03.029"},{"key":"bibr15-0883073814537380","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100222"},{"key":"bibr16-0883073814537380","unstructured":"Cohen BH, Chinnery PF, Copeland WC. 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