TY - JOUR
T1 - Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via cockayne syndrome B protein-mediated transcription-coupled DNA repair
AU - Liu, Su
AU - Yan, Shian Jang
AU - Lee, Yi Fen
AU - Liu, Ning Chun
AU - Ting, Huei Ju
AU - Li, Gonghui
AU - Wu, Qiao
AU - Chen, Lu Min
AU - Chang, Chawnshang
PY - 2011/11/4
Y1 - 2011/11/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M111.259523
DO - 10.1074/jbc.M111.259523
M3 - Article
C2 - 21918225
AN - SCOPUS:80055069189
SN - 0021-9258
VL - 286
SP - 38103
EP - 38108
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -