title: Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair.
abstract: UV irradiation is one of the major external insults to cells and can cause skin aging and cancer. In response to UV light-induced DNA damage, the nucleotide excision repair (NER) pathways are activated to remove DNA lesions. We report here that testicular nuclear receptor 4 (TR4), a member of the nuclear receptor family, modulates DNA repair specifically through the transcription-coupled (TC) NER pathway but not the global genomic NER pathway. The level of Cockayne syndrome B protein (CSB), a member of the TC-NER pathway, is 10-fold reduced in TR4-deficient mouse tissues, and TR4 directly regulates CSB at the transcriptional level. Moreover, restored CSB expression rescues UV hypersensitivity of TR4-deficient cells. Together, these results indicate that TR4 modulates UV sensitivity by promoting the TC-NER DNA repair pathway through transcriptional regulation of CSB. These results may lead to the development of new treatments for UV light-sensitive syndromes, skin cancer, and aging.
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Shian-Jang
authors.initials: SJ
authors.lastname: Yan
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lee
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Ning-Chun
authors.initials: NC
authors.lastname: Liu
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Ting
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Gonghui
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Lab of the Ministry of Education for Cell Biology and Tumor Cell Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan.
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Chen
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642; Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan. Electronic address: chang@urmc.rochester.edu.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000378:metabolism; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D015398:Signal Transduction; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes