Hypoxia-inducible factor-1alpha regulates the expression of nucleotide excision repair proteins in keratinocytes.
Hypoxia-inducible factor-1alpha regulates the expression of nucleotide excision repair proteins in keratinocytes.
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DOI：
10.1093/nar/gkp1072
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Mazurier F
中科院分区：
文献类型：
--
作者：
Rezvani HR;Mahfouf W;Ali N;Chemin C;Ged C;Kim AL;de Verneuil H;Taïeb A;Bickers DR;Mazurier F
DNA修复酶的调控对癌症的预防、发生和治疗至关重要。我们研究了紫外线B （UVB）辐射对人角质形成细胞中两种核苷酸切除修复因子（XPC和XPD）表达的影响。我们发现缺氧诱导因子-1α (HIF-1α)参与了XPC和XPD的调控。早期uvb诱导的HIF-1α的下调增加了XPC mRNA的表达，这是由于HIF-1α和Sp1相互竞争重叠的结合位点。晚期uvb诱导HIF-1α蛋白磷酸化增强，通过直接结合XPC启动子区域单独的缺氧反应元件（HRE）上调XPC mRNA表达。HIF-1α也通过结合其启动子中7个重叠的HREs区域来调节XPD的表达。定量染色质免疫沉淀实验进一步揭示了编码其他DNA修复蛋白（XPB， XPG， CSA和CSB）的基因中可能存在HREs，这表明HIF-1α是DNA修复机制的关键调节因子。对6-4光产物和环丁烷嘧啶二聚体的修复动力学分析也表明，HIF-1α下调导致UVB照射后两种光损伤的立即去除率增加，但后期去除率减弱，这表明HIF-1α在UVB诱导的DNA损伤修复中的功能作用。
The regulation of DNA repair enzymes is crucial for cancer prevention, initiation, and therapy. We have studied the effect of ultraviolet B (UVB) radiation on the expression of the two nucleotide excision repair factors (XPC and XPD) in human keratinocytes. We show that hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of XPC and XPD. Early UVB-induced downregulation of HIF-1α increased XPC mRNA expression due to competition between HIF-1α and Sp1 for their overlapping binding sites. Late UVB-induced enhanced phosphorylation of HIF-1α protein upregulated XPC mRNA expression by direct binding to a separate hypoxia response element (HRE) in the XPC promoter region. HIF-1α also regulated XPD expression by binding to a region of seven overlapping HREs in its promoter. Quantitative chromatin immunoprecipitation assays further revealed putative HREs in the genes encoding other DNA repair proteins (XPB, XPG, CSA and CSB), suggesting that HIF-1α is a key regulator of the DNA repair machinery. Analysis of the repair kinetics of 6-4 photoproducts and cyclobutane pyrimidine dimers also revealed that HIF-1α downregulation led to an increased rate of immediate removal of both photolesions but attenuated their late removal following UVB irradiation, indicating the functional effects of HIF-1α in the repair of UVB-induced DNA damage.
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影响因子：
4.8
作者：
Okino, ST;Chichester, CH;Whitlock, JP
通讯作者：
Whitlock, JP
影响因子：
3.8
作者：
Fitch, ME;Cross, IV;Ford, JA
通讯作者：
Ford, JA
DOI：
10.1073/pnas.202485699
发表时间：
2002-10-01
影响因子：
11.1
作者：
Adimoolam, S;Ford, JM
通讯作者：
Ford, JM
影响因子：
8
作者：
Hanawalt, PC
通讯作者：
Hanawalt, PC
DOI：
10.1016/s0165-7992(85)80018-x
发表时间：
1985-01-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
MITCHELL, DL;HAIPEK, CA;CLARKSON, JM
通讯作者：
CLARKSON, JM