Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions
Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions
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DOI：
10.1016/j.biocel.2011.09.001
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Bevilacqua, Maria Assunta
中科院分区：
文献类型：
--
作者：
Iovine, Barbara;Iannella, Maria Luigia;Bevilacqua, Maria Assunta
损伤特异性 DNA 结合蛋白 1 (DDB1) 是一种多功能蛋白，最初作为异二聚体复合物的亚基被分离出来，该复合物可识别核苷酸切除修复途径中紫外线诱导的 DNA 损伤。 DDB1 和 DDB2 形成促进全局基因组修复 (GG-NER) 的复合物，而 DDB1 和科凯恩综合征 A 组蛋白 (CSA) 形成有助于转录偶联修复 (TC-NER) 途径的复合物。 DDB1 也是泛素-E3 连接酶复合物的组成部分，并作为 Cullin 4A (Cul4A) 和 CUL4 相关因子 (DCAF) 之间的底物或衔接蛋白发挥作用，以实现泛素化的目标底物。 CUL4-DDB1 E3 连接酶复合物调节 DNA 修复、复制和转录中关键蛋白的选择性蛋白水解。此外，DDB1 在紫外线诱导基因的转录调控中发挥作用。可以想象，DDB1 作为损伤传感器来维持基因组完整性和细胞周期进程之间的平衡。然而，这两个事件之间的时间顺序仍有待确定。 (C) 2011 Elsevier Ltd. 保留所有权利。
Damage-specific DNA binding protein 1 (DDB1) is a multifunctional protein that was first isolated as a subunit of a heterodimeric complex that recognises the UV-induced DNA lesions in the nucleotide excision repair pathway. DDB1 and DDB2 form a complex that promotes the global genome repair (GG-NER), whereas DDB1 and Cockayne syndrome group A protein (CSA) form a complex that contributes to the transcription-coupled repair (TC-NER) pathway. DDB1 is also a component of an ubiquitin-E3 ligase complex and functions as substrate or adapter protein between Cullin 4A (Cul4A) and CUL4-associated factors (DCAFs) to target substrates for ubiquitination. CUL4-DDB1 E3-ligase complex regulates the selective proteolysis of key proteins in DNA repair, replication and transcription. In addition, DDB1 plays a role in transcriptional regulation of UV-induced genes. It is conceivable that DDB1 acts as a sensor of damage to maintain the balance between genome integrity and cell cycle progression. However, the temporal order between these two events remains to be established. (C) 2011 Elsevier Ltd. All rights reserved.