p53 is a chromatin accessibility factor for nucleotide excision repair of DNA damage
p53 is a chromatin accessibility factor for nucleotide excision repair of DNA damage
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DOI：
10.1093/emboj/cdg082
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发表时间：
2003-02-17
期刊：
影响因子：
11.4
通讯作者：
Milner, J
中科院分区：
文献类型：
--
作者：
Rubbi, CP;Milner, J
DNA修复中存在时间最长的问题之一是细胞如何松弛染色质以使DNA损伤可用于全局核苷酸切除修复（NER）。由于染色质必须松弛才能有效地检测病变，关键问题是染色质松弛是否先于病变检测，反之亦然。染色质可及性因子已被提出，但尚未确定。在这里，我们表明，p53作为一个染色质可及性因子，介导紫外线诱导的全球染色质松弛。使用本地化的亚核紫外线照射，我们表明，染色质松弛扩展到整个细胞核，这个过程需要p53。我们发现，启动全球NER的序列如下：转录相关的病变检测; p53介导的全球染色质松弛;和全球病变检测。肿瘤抑制因子p53对基因组稳定性至关重要，其促凋亡能力部分解释了这一作用。我们在这里证明，p53也是DNA修复的基本组成部分，在纠正DNA损伤中发挥直接作用。
One of the longest standing problems in DNA repair is how cells relax chromatin in order to make DNA lesions accessible for global nucleotide excision repair (NER). Since chromatin has to be relaxed for efficient lesion detection, the key question is whether chromatin relaxation precedes lesion detection or vice versa. Chromatin accessibility factors have been proposed but not yet identified. Here we show that p53 acts as a chromatin accessibility factor, mediating UV-induced global chromatin relaxation. Using localized subnuclear UV irradiation, we demonstrate that chromatin relaxation is extended over the whole nucleus and that this process requires p53. We show that the sequence for initiation of global NER is as follows: transcription-associated lesion detection; p53-mediated global chromatin relaxation; and global lesion detection. The tumour suppressor p53 is crucial for genomic stability, a role partially explained by its pro-apoptotic capacity. We demonstrate here that p53 is also a fundamental component of DNA repair, playing a direct role in rectifying DNA damage.