Institut de Biologie de l'Ecole Normale Supérieure, Section de Génomique Environnementale et Evolutive, CNRS UMR 8197 INSERM U1021, Paris, France.
EMBO J. 2011 Mar 16;30(6):1162-72. doi: 10.1038/emboj.2011.20. Epub 2011 Feb 8.
Plants and many other eukaryotes can make use of two major pathways to cope with mutagenic effects of light, photoreactivation and nucleotide excision repair (NER). While photoreactivation allows direct repair by photolyase enzymes using light energy, NER requires a stepwise mechanism with several protein complexes acting at the levels of lesion detection, DNA incision and resynthesis. Here we investigated the involvement in NER of DE-ETIOLATED 1 (DET1), an evolutionarily conserved factor that associates with components of the ubiquitylation machinery in plants and mammals and acts as a negative repressor of light-driven photomorphogenic development in Arabidopsis. Evidence is provided that plant DET1 acts with CULLIN4-based ubiquitin E3 ligase, and that appropriate dosage of DET1 protein is necessary for efficient removal of UV photoproducts through the NER pathway. Moreover, DET1 is required for CULLIN4-dependent targeted degradation of the UV-lesion recognition factor DDB2. Finally, DET1 protein is degraded concomitantly with DDB2 upon UV irradiation in a CUL4-dependent mechanism. Altogether, these data suggest that DET1 and DDB2 cooperate during the excision repair process.
植物和许多其他真核生物可以利用两种主要途径来应对光的诱变效应，光复活和核苷酸切除修复（NER）。虽然光复活允许光裂合酶酶利用光能直接修复，但 NER 需要一个逐步的机制，几个蛋白质复合物在损伤检测、DNA 切口和重新合成的水平上发挥作用。在这里，我们研究了 DE-ETIOLATED 1（DET1）在 NER 中的参与，DET1 是一种进化上保守的因子，它与植物和哺乳动物的泛素化机制的成分相关联，并作为拟南芥中光驱动光形态发生发育的负调节因子。有证据表明，植物 DET1 与基于 CULLIN4 的泛素 E3 连接酶一起作用，并且适当剂量的 DET1 蛋白对于通过 NER 途径有效去除 UV 光产物是必要的。此外，DET1 对于 CULLIN4 依赖性靶向降解 UV 损伤识别因子 DDB2 是必需的。最后，DET1 蛋白在 UV 照射下与 DDB2 一起在 CUL4 依赖性机制中降解。总之，这些数据表明 DET1 和 DDB2 在切除修复过程中合作。
