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

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