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Biallelic\n                    <jats:italic>PARN<\/jats:italic>\n                    mutations were associated with H\u00f8yeraal\u2013Hreidarsson (HH) syndrome, a rare telomere biology disorder that, because of its severity, is likely not exclusively due to h\n                    <jats:italic>TR<\/jats:italic>\n                    down\u2010regulation. Whether PARN deficiency was affecting the expression of telomere\u2010related genes was still unclear. Using cells from two unrelated HH individuals carrying novel\n                    <jats:italic>PARN<\/jats:italic>\n                    mutations and a human PARN knock\u2010out (KO) cell line with inducible\n                    <jats:italic>PARN<\/jats:italic>\n                    complementation, we found that PARN deficiency affects both telomere length and stability and down\u2010regulates the expression of\n                    <jats:italic>TRF1<\/jats:italic>\n                    ,\n                    <jats:italic>TRF2<\/jats:italic>\n                    ,\n                    <jats:italic>TPP1<\/jats:italic>\n                    ,\n                    <jats:italic>RAP1<\/jats:italic>\n                    , and\n                    <jats:italic>POT1<\/jats:italic>\n                    shelterin transcripts. Down\u2010regulation of dyskerin\u2010encoding\n                    <jats:italic>DKC1<\/jats:italic>\n                    mRNA was also observed and found to result from p53 activation in PARN\u2010deficient cells. We further showed that PARN deficiency compromises ribosomal RNA biogenesis in patients' fibroblasts and cells from heterozygous\n                    <jats:italic>Parn<\/jats:italic>\n                    KO mice. Homozygous\n                    <jats:italic>Parn<\/jats:italic>\n                    KO however resulted in early embryonic lethality that was not overcome by\n                    <jats:italic>p53<\/jats:italic>\n                    KO. Our results refine our knowledge on the pleiotropic cellular consequences of PARN deficiency.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201810201","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T17:45:14Z","timestamp":1559843114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Impaired telomere integrity and rRNA biogenesis in PARN\u2010deficient patients and knock\u2010out models"],"prefix":"10.1038","volume":"11","author":[{"given":"Maname","family":"Benyelles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harikleia","family":"Episkopou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Fran\u00e7oise","family":"O'Donohue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00ebtitia","family":"Kermasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Frange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Poulain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Burcu Belen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meltem","family":"Polat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bole\u2010Feysot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francina","family":"Langa\u2010Vives","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Emmanuel","family":"Gleizes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"de Villartay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Callebaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-2527","authenticated-orcid":false,"given":"Anabelle","family":"Decottignies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-8022","authenticated-orcid":false,"given":"Patrick","family":"Revy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"BFEMMM201810201_CR1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nature02118","volume":"426","author":"F d'Adda di Fagagna","year":"2003","unstructured":"d'Adda di Fagagna F, Reaper PM, Clay\u2010Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere\u2010initiated senescence. 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