SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair

Abstract

XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. However, the exact regulatory function of these modifications in vivo remains elusive. Here we show that RNF111 is required for efficient repair of ultraviolet-induced DNA lesions. RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation, and is needed for stable incorporation of the NER endonucleases XPG and ERCC1/XPF. Our data suggest that RNF111, together with the CRL4DDB2 ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction, thereby providing an extra layer of quality control of NER.

Controllable Synthesis of Graphene by Plasma‐Enhanced Chemical Vapor Deposition and Its Related Applications

“…However, graphene/h‐BN devices fabricated by mechanical transfer normally suffer from unstable electrical performance due to chemical contamination, structure defects and uncertain alignment between graphene and h‐BN. Instead, graphene/h‐BN hetero‐structures are fabricated by CVD techniques 58, 59, 60, 61, 62, 63. The precise alignment between grown graphene and h‐BN provides more favorable device characters.…”

“…For example, theoretical calculations predicts that AB stacked graphene/h‐BN could open a band gap of 53 meV in graphene 56. Recently, large single‐crystalline graphene domains up to 20 μm can be synthesized on h‐BN with the a gaseous catalyst silane 63. The Hall mobility can reach 20 000 cm 2 V −1 s −1 and the secondary Dirac cone can be observed due to the moiré pattern.…”

Role of Deubiquitinating Enzymes in DNA Repair

“…Ubiquitination is mediated by UBC13/MMS2 E2-conjugating enzyme, suggesting that it is likely a nonproteolytic K63-linked polyubiquitination event. Interestingly, RNF111-mediated polyubiquitination induces the release of XPC from the lesions (209,210), which is the opposite effect of CUL4-DDB2 mediated polyubiquitination. Both DDB2 and RNF111 depletion impair the UV-induced DNA repair, suggesting a model in which two sequential polyubiquitination events on XPC regulate the recruitment and release of XPC during NER.…”

“…Regulating XPC loading onto chromatin by polyubiquitination appears to be a key event in the GG-NER. XPC is ubiquitinated by two E3 ubiquitin ligases, CUL4-DDB2 (208) and RNF111 (209,210). The CUL4-DDB2 E3 ligase polyubiquitinates XPC and does not lead to proteasomal degradation but rather promotes increased binding affinity of XPC to DNA (208).…”

“…Both DDB2 and RNF111 depletion impair the UV-induced DNA repair, suggesting a model in which two sequential polyubiquitination events on XPC regulate the recruitment and release of XPC during NER. The RNF111-induced release of XPC from chromatin is required for recruitment of downstream NER factors and completion of repair (210). A recent study found that USP7 directly binds to and deubiquitinates XPC and that UV-induced XPC degradation is accelerated in USP7 Ϫ/Ϫ HCT116 cells (211).…”