The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions

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• 作者：Moser ; Jill ; Volker ; Marcel ; Kool ; Hanneke ; Alekseev ; Sergei ; Vrieling ; Harry ; Yasui ; Akira ; et. al.
• 关键词：UV-damaged DNA binding protein ; Xeroderma pigmentosum group E ; 6-4 Photoproducts ; Cylcobutane pyrimidine dimmers ; Nucleotide excision repair
• 刊名：DNA Repair
• 出版年：2005
• 出版时间：May 2, 2005
• 年：2005
• 卷：4
• 期：5
• 页码：571-582
• 全文大小：424 K

文摘

Previous studies point to the XPC-hHR23B complex as the principal initiator of global genome nucleotide excision repair (NER) pathway, responsible for the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) in human cells. However, the UV-damaged DNA binding protein (UV-DDB) has also been proposed as a damage recognition factor involved in repair of UV-photoproducts, especially CPD. Here, we show in human XP-E cells (UV-DDB deficient) that the incision complex formation at UV-induced lesions was severely diminished in locally damaged nuclear spots. Repair kinetics of CPD and 6-4PP in locally and globally UV-irradiated normal human and XP-E cells demonstrate that UV-DDB can mediate efficient targeting of XPC-hHR23B and other NER factors to 6-4PP. The data is consistent with a mechanism in which UV-DDB forms a stable complex when bound to a 6-4PP, allowing subsequent repair proteins – starting with XPC-hHR23B – to accumulate, and verify the lesion, resulting in efficient 6-4PP repair. These findings suggest that (i) UV-DDB accelerates repair of 6-4PP, and at later time points also CPD, (ii) the fraction of 6-4PP that can be bound by UV-DDB is limited due to its low cellular quantity and fast UV dependent degradation, and (iii) in the absence of UV-DDB a slow XPC-hHR23B dependent pathway is capable to repair 6-4PP, and to some extent also CPD.