{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:37Z","timestamp":1791267157780,"version":"4.1.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aborted DNA ligation events in eukaryotic cells can generate 5\u2032-adenylated (5\u2032-AMP) DNA termini that can be removed from DNA by aprataxin (APTX). Mutations in\n                    <jats:italic>APTX<\/jats:italic>\n                    cause an inherited human disease syndrome characterized by early-onset progressive ataxia with ocular motor apraxia (AOA1). APTX is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders the mitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well elucidated. Here, we monitored the repair of 5\u2032-AMP DNA damage in nuclear and mitochondrial extracts from human\n                    <jats:italic>APTX<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    and\n                    <jats:italic>APTX<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cells. The efficiency of repair of 5\u2032-AMP DNA was much lower in mitochondrial than in nuclear protein extracts and resulted in persistent DNA repair intermediates in APTX deficient cells. Moreover, the removal of 5\u2032-AMP from DNA was significantly slower in the mitochondrial extracts from human cell lines and mouse tissues compared with their corresponding nuclear extracts. These results suggest that, contrary to nuclear DNA repair, mitochondrial DNA repair is not able to compensate for APTX deficiency resulting in the accumulation of mitochondrial DNA damage.\n                  <\/jats:p>","DOI":"10.1038\/srep12876","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T06:46:22Z","timestamp":1439189182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Slow mitochondrial repair of 5\u2032-AMP renders mtDNA susceptible to damage in APTX deficient cells"],"prefix":"10.1038","volume":"5","author":[{"given":"Mansour","family":"Akbari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sykora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilhelm A.","family":"Bohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,10]]},"reference":[{"key":"BFsrep12876_CR1","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.1074\/jbc.M507946200","volume":"281","author":"AW Kijas","year":"2006","unstructured":"Kijas, A. W., Harris, J. L., Harris, J. M. & Lavin, M. F. Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA\/RNA binding and nucleotide hydrolase activities. J Biol Chem 281, 13939\u201313948 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep12876_CR2","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/nrg2380","volume":"9","author":"KW Caldecott","year":"2008","unstructured":"Caldecott, K. W. Single-strand break repair and genetic disease. Nat Rev Genet 9, 619\u2013631 (2008).","journal-title":"Nat Rev Genet"},{"key":"BFsrep12876_CR3","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ng1001-184","volume":"29","author":"H Date","year":"2001","unstructured":"Date, H. et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. 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