{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:12:52Z","timestamp":1790338372943,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,4]],"date-time":"2013-09-04T00:00:00Z","timestamp":1378252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2013,9,4]],"date-time":"2013-09-04T00:00:00Z","timestamp":1378252800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    oats plus is a rare recessive disorder characterized by intracranial calcifications, hematological abnormalities, and retinal vascular defects. This disease results from mutations in\n                    <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                    1, a member of the\n                    <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                    1\u2013\n                    <jats:styled-content style=\"fixed-case\">STN<\/jats:styled-content>\n                    1\u2013\n                    <jats:styled-content style=\"fixed-case\">TEN<\/jats:styled-content>\n                    1 (\n                    <jats:styled-content style=\"fixed-case\">CST<\/jats:styled-content>\n                    ) complex critical for telomere replication. Telomeres are specialized\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    \/protein structures essential for the maintenance of genome stability. Several patients with\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    oats plus display critically shortened telomeres, suggesting that telomere dysfunction plays an important role in disease pathogenesis. These patients inherit\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                      1\n                    <\/jats:italic>\n                    mutations in a compound heterozygous manner, with one allele encoding a frameshift mutant and the other a missense mutant. How these mutations impact upon telomere function is unknown. We report here the first biochemical characterization of human\n                    <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                    1 mutations. We found that all\n                    <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                    1 frameshift mutations generated truncated or unstable protein products, none of which were able to form a complex with\n                    <jats:styled-content style=\"fixed-case\">STN<\/jats:styled-content>\n                    1\u2013\n                    <jats:styled-content style=\"fixed-case\">TEN<\/jats:styled-content>\n                    1 on telomeres, resulting in progressive telomere shortening and formation of fused chromosomes. Missense mutations are able to form the\n                    <jats:styled-content style=\"fixed-case\">CST<\/jats:styled-content>\n                    complex at telomeres, but their expression levels are often repressed by the frameshift mutants. Our results also demonstrate for the first time that\n                    <jats:styled-content style=\"fixed-case\">CTC<\/jats:styled-content>\n                    1 mutations promote telomere dysfunction by decreasing the stability of\n                    <jats:styled-content style=\"fixed-case\">STN<\/jats:styled-content>\n                    1 to reduce its ability to interact with\n                    <jats:styled-content style=\"fixed-case\">DNA P<\/jats:styled-content>\n                    ol\u03b1, thus highlighting a previously unknown mechanism to induce telomere dysfunction.\n                  <\/jats:p>","DOI":"10.1111\/acel.12139","type":"journal-article","created":{"date-parts":[[2013,7,22]],"date-time":"2013-07-22T05:35:52Z","timestamp":1374471352000},"page":"1100-1109","source":"Crossref","is-referenced-by-count":72,"title":["Functional characterization of human\n                    <scp>CTC<\/scp>\n                    1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease\n                    <scp>C<\/scp>\n                    oats plus"],"prefix":"10.1111","volume":"12","author":[{"given":"Peili","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Yale University School of Medicine 330 Cedar Street New Haven CT 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Yale University School of Medicine 330 Cedar Street New Haven CT 06520 USA"},{"name":"Department of Pathology Yale University School of Medicine 330 Cedar Street New Haven CT 06520 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