{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:18:28Z","timestamp":1790759908402,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC","doi-asserted-by":"publisher","award":["ARCPJA2021060003938"],"award-info":[{"award-number":["ARCPJA2021060003938"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mice with a constitutive increase in p53 activity exhibited features of dyskeratosis congenita (DC), a bone marrow failure syndrome (BMFS) caused by defective telomere maintenance. Further studies confirmed, in humans and mice, that germline mutations affecting TP53 or its regulator MDM4 may cause short telomeres and alter hematopoiesis, but also revealed features of Diamond\u2013Blackfan anemia (DBA) or Fanconi anemia (FA), two BMFSs, respectively, caused by defects in ribosomal function or DNA repair. p53 downregulates several genes mutated in DC, either by binding to promoter sequences (DKC1) or indirectly via the DREAM repressor complex (RTEL1, DCLRE1B), and the p53-DREAM pathway represses 22 additional telomere-related genes. Interestingly, mutations in any DC-causal gene will cause telomere dysfunction and subsequent p53 activation to further promote the repression of p53-DREAM targets. Similarly, ribosomal dysfunction and DNA lesions cause p53 activation, and p53-DREAM targets include the DBA-causal gene TSR2, at least 9 FA-causal genes, and 38 other genes affecting ribosomes or the FA pathway. Furthermore, patients with BMFSs may exhibit brain abnormalities, and p53-DREAM represses 16 genes mutated in microcephaly or cerebellar hypoplasia. In sum, positive feedback loops and the repertoire of p53-DREAM targets likely contribute to partial phenotypic overlaps between BMFSs of distinct molecular origins.<\/jats:p>","DOI":"10.3390\/ijms241914940","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:49:29Z","timestamp":1696578569000},"page":"14940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["p53 in the Molecular Circuitry of Bone Marrow Failure Syndromes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1218-4921","authenticated-orcid":false,"given":"Jeanne","family":"Rakotopare","sequence":"first","affiliation":[{"name":"Genetics of Tumor Suppression, Institut Curie, CEDEX 05, 75248 Paris, France"},{"name":"CNRS UMR3244, 75005 Paris, France"},{"name":"Faculty of Science and Engineering, Sorbonne University, 75005 Paris, France"},{"name":"Institut Curie, PSL Research University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-4106","authenticated-orcid":false,"given":"Franck","family":"Toledo","sequence":"additional","affiliation":[{"name":"Genetics of Tumor Suppression, Institut Curie, CEDEX 05, 75248 Paris, France"},{"name":"CNRS UMR3244, 75005 Paris, France"},{"name":"Faculty of Science and Engineering, Sorbonne University, 75005 Paris, France"},{"name":"Institut Curie, PSL Research University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/342705a0","article-title":"Mutations in the P53 Gene Occur in Diverse Human Tumour Types","volume":"342","author":"Nigro","year":"1989","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1126\/science.1978757","article-title":"Germ Line P53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms","volume":"250","author":"Malkin","year":"1990","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/460466a","article-title":"Cancer: Three Birds with One Stone","volume":"460","author":"Toledo","year":"2009","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1093\/nar\/19.19.5191","article-title":"A DNA Binding Domain Is Contained in the C-Terminus of Wild Type P53 Protein","volume":"19","author":"Foord","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nrc2012","article-title":"Regulating the P53 Pathway: In Vitro Hypotheses, in Vivo Veritas","volume":"6","author":"Toledo","year":"2006","journal-title":"Nat. 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