{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:12:27Z","timestamp":1791997947601,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["ESF\/14-BM-A55-0001\/18"],"award-info":[{"award-number":["ESF\/14-BM-A55-0001\/18"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013859","name":"Damp Stiftung","doi-asserted-by":"publisher","award":["2017-05"],"award-info":[{"award-number":["2017-05"]}],"id":[{"id":"10.13039\/501100013859","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG EM 63\/13-1"],"award-info":[{"award-number":["DFG EM 63\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and 6,4-pyrimidine-pyrimidone dimers (6,4-PPs). Alterations in genes of the NER can lead to DNA damage repair disorders such as Xeroderma pigmentosum (XP). XP is a rare autosomal recessive genetic disorder associated with UV-sensitivity and early onset of skin cancer. Recently, extensive research has been conducted on the functional relevance of splice variants and their relation to cancer. Here, we focus on the functional relevance of alternative splice variants of XP genes.<\/jats:p>","DOI":"10.3390\/genes12081173","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T10:47:46Z","timestamp":1627555666000},"page":"1173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Xeroderma Pigmentosum: Gene Variants and Splice Variants"],"prefix":"10.3390","volume":"12","author":[{"given":"Marie Christine","family":"Martens","sequence":"first","affiliation":[{"name":"Clinic and Policlinic for Dermatology and Venerology, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Emmert","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Dermatology and Venerology, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0098-6546","authenticated-orcid":false,"given":"Lars","family":"Boeckmann","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Dermatology and Venerology, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Photocarcinogenesis and Skin Cancer Prevention Strategies: An Update","volume":"38","author":"Martens","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrm3822","article-title":"Understanding nucleotide excision repair and its roles in cancer and ageing","volume":"15","author":"Marteijn","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/cge.13545","article-title":"Heterogeneity and overlaps in nucleotide excision repair disorders","volume":"97","author":"Ferri","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/carcin\/21.3.453","article-title":"Nucleotide excision repair and human syndromes","volume":"21","author":"Hoeijmakers","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_5","first-page":"867","article-title":"Xeroderma pigmentosum: Diagnostic procedures, interdisciplinary patient care, and novel therapeutic approaches","volume":"12","author":"Lehmann","year":"2014","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1055\/s-0043-123031","article-title":"Xeroderma pigmentosum\u2014Facts and Perspectives","volume":"44","author":"Lehmann","year":"2018","journal-title":"Aktuelle Derm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Martens, M.C., Emmert, S., and Boeckmann, L. (2020). Sunlight, Vitamin D, and Xeroderma Pigmentosum, Springer.","DOI":"10.1007\/978-3-030-46227-7_16"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1007\/s00018-009-8737-y","article-title":"Nucleotide excision repair: Variations on versatility","volume":"66","author":"Nouspikel","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/s41467-020-15903-8","article-title":"The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II","volume":"11","author":"Mevissen","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Borsz\u00e9kov\u00e1 Pulzov\u00e1, L., Ward, T.A., and Chovanec, M. (2020). XPA: DNA Repair Protein of Significant Clinical Importance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062182"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nature23903","article-title":"The cryo-electron microscopy structure of human transcription factor IIH","volume":"549","author":"Greber","year":"2017","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1001\/archderm.1994.01690080084012","article-title":"The Role of Sunlight and DNA Repair in Melanoma and Nonmelanoma Skin Cancer: The Xeroderma Pigmentosum Paradigm","volume":"130","author":"Kraemer","year":"1994","journal-title":"Arch. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1136\/jmg.2010.083022","article-title":"Cancer and Neurologic Degeneration in Xeroderma","volume":"48","author":"Bradford","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1111\/bph.14557","article-title":"Xeroderma pigmentosum: Overview of pharmacology and novel therapeutic strategies for neurological symptoms","volume":"176","author":"Abeti","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijwd.2015.05.003","article-title":"De Sanctis\u2013Cacchione syndrome: A case report and literature review","volume":"1","author":"Rahbar","year":"2015","journal-title":"Int. J. Women\u2019s Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E1236","DOI":"10.1073\/pnas.1519444113","article-title":"Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect","volume":"113","author":"Fassihi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/bjd.13577","article-title":"Importance of genotype-phenotype correlation in xeroderma pigmentosum","volume":"172","author":"Fassihi","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/ejhg.2013.233","article-title":"Clinical utility gene card for: Xeroderma pigmentosum","volume":"22","author":"Schubert","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3389\/fgene.2019.00495","article-title":"Whole-Exome Sequencing Enables the Diagnosis of Variant-Type Xeroderma Pigmentosum","volume":"10","author":"Fang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145523","DOI":"10.1016\/j.gene.2021.145523","article-title":"Role of promoters in regulating alternative splicing","volume":"782","author":"Kolathur","year":"2021","journal-title":"Gene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100728","DOI":"10.1016\/j.drup.2020.100728","article-title":"The role of alternative splicing in cancer: From oncogenesis to drug resistance","volume":"53","author":"Sciarrillo","year":"2020","journal-title":"Drug Resist. Updat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.pharmthera.2012.08.005","article-title":"Alternative transcription and alternative splicing in cancer","volume":"136","author":"Pal","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nmeth.3828","article-title":"Protein isoforms: More than meets the eye","volume":"13","author":"Larochelle","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14453","DOI":"10.1038\/s41598-020-71221-5","article-title":"Pathogenic impact of transcript isoform switching in 1,209 cancer samples covering 27 cancer types using an isoform-specific interaction network","volume":"10","author":"Kahraman","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6935","DOI":"10.1038\/s41388-020-01479-6","article-title":"Role of androgen receptor splice variant-7 (AR-V7) in prostate cancer resistance to 2nd-generation androgen receptor signaling inhibitors","volume":"39","author":"Zhu","year":"2020","journal-title":"Oncogene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18550","DOI":"10.18632\/oncotarget.14537","article-title":"Androgen receptor splice variants and prostate cancer: From bench to bedside","volume":"8","author":"Wadosky","year":"2017","journal-title":"Oncotarget"},{"key":"ref_27","first-page":"1875","article-title":"Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy","volume":"52","author":"Mortensen","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1016\/j.cellsig.2014.07.011","article-title":"Regulation of alternative splicing of CD44 in cancer","volume":"26","author":"Prochazka","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/CM9.0000000000000542","article-title":"Significance of alternative splicing in cancer cells","volume":"133","author":"Qi","year":"2020","journal-title":"Chin. Med. J. (Engl.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fimmu.2020.00099","article-title":"CAR T Cells Redirected to CD44v6 Control Tumor Growth in Lung and Ovary Adenocarcinoma Bearing Mice","volume":"11","author":"Porcellini","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature10662","article-title":"RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)","volume":"480","author":"Poulikakos","year":"2011","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1038\/s41467-020-18123-2","article-title":"Inhibitors of BRAF dimers using an allosteric site","volume":"11","author":"Agianian","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","unstructured":"Sch\u00e4rer, O.D. (2008). XPG: Its Products and Biological Roles. Molecular Mechanisms of Xeroderma Pigmentosum, Springer."},{"key":"ref_34","first-page":"783","article-title":"Forschung zu Genodermatosen durch neue Genom- Editing -Methoden","volume":"15","author":"Lehmann","year":"2017","journal-title":"JDDG J. Dtsch. Dermatol. Ges."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nbt.2647","article-title":"DNA targeting specificity of RNA-guided Cas9 nucleases","volume":"31","author":"Hsu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Martens, M.C., Edelkamp, J., Seebode, C., Sch\u00e4fer, M., St\u00e4hlke, S., Krohn, S., Jung, O., Murua Escobar, H., Emmert, S., and Boeckmann, L. (2021). Generation and Characterization of a CRISPR\/Cas9-Mediated SNAP29 Knockout in Human Fibroblasts. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105293"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1007\/s00018-017-2455-7","article-title":"XPF knockout via CRISPR\/Cas9 reveals that ERCC1 is retained in the cytoplasm without its heterodimer partner XPF","volume":"74","author":"Lehmann","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.18632\/oncotarget.23105","article-title":"Splice variants of the endonucleases XPF and XPG contain residual DNA repair capabilities and could be a valuable tool for personalized medicine","volume":"9","author":"Lehmann","year":"2018","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1093\/nar\/29.7.1443","article-title":"The human XPG gene: Gene architecture, alternative splicing and single nucleotide polymorphisms","volume":"29","author":"Emmert","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1093\/nar\/gkf469","article-title":"The human XPC DNA repair gene: Arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function","volume":"30","author":"Khan","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12935-020-01244-5","article-title":"Association of human XPA rs1800975 polymorphism and cancer susceptibility: An integrative analysis of 71 case\u2013control studies","volume":"20","author":"Yuan","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1089\/gtmb.2013.0267","article-title":"Association of XPC Gene Polymorphisms with Susceptibility to Prostate Cancer: Evidence from 3936 Subjects","volume":"17","author":"Zou","year":"2013","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152548","DOI":"10.1016\/j.prp.2019.152548","article-title":"Genetic variants of DNA repair pathway genes on lung cancer risk","volume":"215","author":"Li","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fmolb.2018.00023","article-title":"XPD\u2013The Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis","volume":"5","author":"Sameer","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e6832","DOI":"10.1097\/MD.0000000000006832","article-title":"Association between common polymorphisms in ERCC gene and glioma risk","volume":"96","author":"Qian","year":"2017","journal-title":"Medicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86621","DOI":"10.18632\/oncotarget.13361","article-title":"Associations between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16765","DOI":"10.3748\/wjg.v20.i44.16765","article-title":"Xeroderma pigmentosum group D polymorphisms and esophageal cancer susceptibility: A meta-analysis based on case-control studies","volume":"20","author":"Yang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.gene.2014.01.049","article-title":"The effect of XPD\/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis","volume":"538","author":"Liu","year":"2014","journal-title":"Gene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e7467","DOI":"10.1097\/MD.0000000000007467","article-title":"The association between XPG polymorphisms and cancer susceptibility","volume":"96","author":"Han","year":"2017","journal-title":"Medicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/carcin\/bgi055","article-title":"Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: A case\u2013control study","volume":"26","author":"Blankenburg","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_52","first-page":"3321","article-title":"An intronic poly (AT) polymorphism of the DNA repair gene XPC and risk of squamous cell carcinoma of the head and neck: A case-control study","volume":"61","author":"Shen","year":"2001","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"629266","DOI":"10.3389\/fphar.2020.629266","article-title":"DNA Repair Pathways in Cancer Therapy and Resistance","volume":"11","author":"Li","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:44Z","timestamp":1760164604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["genes12081173"],"URL":"https:\/\/doi.org\/10.3390\/genes12081173","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}