The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts
The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts
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DOI：
10.1016/s1568-7864(03)00066-1
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发表时间：
2003-07-16
期刊：
影响因子：
3.8
通讯作者：
Ford, JA
中科院分区：
文献类型：
--
作者：
Fitch, ME;Cross, IV;Ford, JA
肿瘤抑制蛋白p53在许多细胞对UV诱导的DNA损伤的反应中起作用，包括激活全局核苷酸切除修复（NER）途径。影响NER的一个潜在机制是通过p53转录调节直接参与NER的基因的能力。DDB 2就是这样一种基因，它在基础水平和紫外线诱导水平上都受到p53的调节。为了进一步了解p53在NER中的作用，我们转染并选择了在人p53缺陷细胞系中稳定过表达DDB2的克隆。与对照相比，环丁烷嘧啶二聚体的全局基因组修复（GGR）在DDB2表达细胞中显著增加，表明p53 wt蛋白本身不是有效GGR直接需要的。DDB2的蛋白质产物p48也通过响应于UV照射的蛋白酶体降解进行后调节。p48在转录水平上受p53的调节，以及在转录后受蛋白酶体的调节，表明p48可能是NER的限速成分。(C)2003 Elsevier Science B.V.保留所有权利。
The tumor suppressor protein p53 functions in many cellular responses to UV-induced DNA damage, including activating the global nucleotide excision repair (NER) pathway. A potential mechanism for the effect on NER is through the ability of p53 to transcriptionally regulate genes that are directly involved in NER. DDB2 is one such gene that is regulated by p53 at both the basal and UV inducible levels. In order to further understand p53's role in NER, we transfected and selected clones that stably overexpress DDB2 in a human p53 deficient cell line. Global genomic repair (GGR) of cyclobutane pyrimidine dimers was significantly increased in the DDB2 expressing cells in comparison to controls, demonstrating that p53 wt protein itself is not directly required for efficient GGR. The protein product of DDB2, p48, is also post-translationally regulated by proteasomal degradation in response to UV irradiation. The regulation of p48 at both the transcriptional level by p53, and post-translationally by the proteasome suggests that p48 may be a rate limiting component of NER. (C) 2003 Elsevier Science B.V. All rights reserved.