{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:05:58Z","timestamp":1779213958489,"version":"3.51.4"},"reference-count":23,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:p>\n                    DNA damage and repair are central to the onset of cancer, aging, and aging-related diseases. Rare genetic defects in the nucleotide excision repair pathway, such as those causing the cancer-prone disorder xeroderma pigmentosum (XP) or the progeroid condition Cockayne syndrome, highlight the dramatic consequences of unrepaired DNA lesions. In this issue of the\n                    <jats:italic>JCI<\/jats:italic>\n                    , two related papers from Ogi and coworkers \u2014 Fassihi et al. and Nakazawa et al. \u2014 describe a new XP clinical entity, XP-J, linked to a pathogenic variant in the p52 subunit of the transcription-repair complex TFIIH. The studies\u2019 characterization of XP-J and the p52\u0394C variant opened unexpected possibilities to ameliorate the molecular defect in another subunit of TFIIH that causes a different, more severe repair syndrome: trichothiodystrophy. This commentary provides a broader historical, medical, and molecular context for the intricate genotype-phenotype relationship between compromised repair and its clinical consequences and discusses next steps for the advances reported.\n                  <\/jats:p>","DOI":"10.1172\/jci199822","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T19:00:52Z","timestamp":1763319652000},"source":"Crossref","is-referenced-by-count":2,"title":["Expanding the landscape of nucleotide excision repair disorders: from discovery to therapy"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-1681","authenticated-orcid":true,"given":"Arjan F.","family":"Theil","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan H.J.","family":"Hoeijmakers","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands."},{"name":"University Hospital of Cologne, CECAD Forschungszentrum, Institute for Genome Stability in Aging and Disease, K\u00f6ln, Germany."},{"name":"Princess Maxima Center for Pediatric Oncology, Oncode Institute, Utrecht, Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3822"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012609"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-025-01715-9"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102907"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2013.02.006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2025.108555"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2023.103568"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13545"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI195731"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI195732"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/218652a0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/newbio238080a0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.1.219"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.7.768"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/phpp.12108"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nature19329"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00411-4"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01279-6"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.104105"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/biom15071026"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.07.008"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/81603"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003431"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/199822\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:08:29Z","timestamp":1779210509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/199822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":23,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,9,9]]},"published-print":{"date-parts":[[2025,11,17]]}},"alternative-id":["10.1172\/JCI199822"],"URL":"https:\/\/doi.org\/10.1172\/jci199822","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"article-number":"e199822"}}