Inhaltszusammenfassung

The genome of cellular systems is under constant threat of genotoxic agents. Thus, efficient DNA damage repair is essential to maintain integrity and stability of the genome. Nucleotide excision repair (NER) represents one of the main cellular DNA repair pathways induced by UV light exposure. The global genome-NER branch counteracting lesions in transcriptionally silent DNA regions, is initiated by binding of the damage recognition factor XPC to DNA damage. The UV-DDB-CULA-RBX1 E3 ligase cata...The genome of cellular systems is under constant threat of genotoxic agents. Thus, efficient DNA damage repair is essential to maintain integrity and stability of the genome. Nucleotide excision repair (NER) represents one of the main cellular DNA repair pathways induced by UV light exposure. The global genome-NER branch counteracting lesions in transcriptionally silent DNA regions, is initiated by binding of the damage recognition factor XPC to DNA damage. The UV-DDB-CULA-RBX1 E3 ligase catalyzed polyubiquitylation of XPC after UV irradiation has been well studied. However, mechanistic insight into how ubiquitylated XPC regulates the GG-NER pathway is still lacking. Here, we show that ubiquitylated XPC is associated with a novel protein complex consisting of the heterodimeric ERCC1-XPF endonuclease and the deubiquitylase USP7 (also known as HAUSP). Interestingly, ERCC1-XPF enhances the deubiquitylation reaction of XPC in vitro and in vivo. We further demonstrate that USP7 competes with XPA for binding to the ERCC1-XPF endonuclease complex. Collectively our results provide evidence of two distinct ERCC1-XPF protein complexes that operate in 5' DNA incision or in XPC deubiquitylation thus coupling both processes in the GG-NER pathway.» weiterlesen» einklappen

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DDC Sachgruppe:
Allgemeines, Wissenschaft