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.
| Original language | English |
|---|---|
| Pages (from-to) | 38103-38108 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 44 |
| DOIs | |
| Publication status | Published - 2011 Nov 4 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via cockayne syndrome B protein-mediated transcription-coupled DNA repair. / Liu, Su; Yan, Shian-Jang; Lee, Yi Fen; Liu, Ning Chun; Ting, Huei Ju; Li, Gonghui; Wu, Qiao; Chen, Lu Min; Chang, Chawnshang.
In: Journal of Biological Chemistry, Vol. 286, No. 44, 04.11.2011, p. 38103-38108.Research output: Contribution to journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=80055069189&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80055069189&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.259523
DO - 10.1074/jbc.M111.259523
M3 - Article
C2 - 21918225
AN - SCOPUS:80055069189
VL - 286
SP - 38103
EP - 38108
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 44
ER -