E2F1 Localizes to Sites of UV-induced DNA Damage to Enhance Nucleotide Excision Repair
E2F1 Localizes to Sites of UV-induced DNA Damage to Enhance Nucleotide Excision Repair
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DOI：
10.1074/jbc.m110.121939
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发表时间：
2010-06-18
影响因子：
4.8
通讯作者：
Johnson, David G.
中科院分区：
文献类型：
--
作者：
Guo, Ruifeng;Chen, Jie;Johnson, David G.
E2F1转录因子是众所周知的细胞增殖和凋亡调节因子，但其在DNA损伤反应中的作用尚不清楚。使用局部紫外线照射技术和免疫荧光染色，E2F1 显示在 DNA 损伤部位积聚。 E2F1 定位到紫外线损伤的 DNA 需要 ATM 和 Rad3 相关 (ATR) 激酶以及 E2F1 的丝氨酸 31，但不需要完整的 DNA 结合域。 E2F1 缺陷似乎不会影响核苷酸切除修复 (NER) 因子（例如 XPC 和 XPA）的表达。然而，E2F1 缺失确实会损害 NER 因子向损伤部位的募集，并降低 DNA 修复的效率。无法结合 DNA 或激活转录的 E2F1 突变体保留了刺激 NER 的能力。这些发现表明，E2F1 在 DNA 修复中具有直接的非转录作用，涉及增加 NER 因子向损伤位点的募集。
The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in the DNA damage response is less clear. Using a local UV irradiation technique and immunofluorescence staining, E2F1 is shown to accumulate at sites of DNA damage. Localization of E2F1 to UV-damaged DNA requires the ATM and Rad3-related (ATR) kinase and serine 31 of E2F1 but not an intact DNA binding domain. E2F1 deficiency does not appear to affect the expression of nucleotide excision repair (NER) factors, such as XPC and XPA. However, E2F1 depletion does impair the recruitment of NER factors to sites of damage and reduces the efficiency of DNA repair. E2F1 mutants unable to bindDNAor activate transcription retain the ability to stimulate NER. These findings demonstrate that E2F1 has a direct, non-transcriptional role in DNA repair involving increased recruitment of NER factors to sites of damage.