SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair.

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.

Differential binding kinetics of replication protein A during replication and the pre- and post-incision steps of nucleotide excision repair.

The ability of replication protein A (RPA) to bind single-stranded DNA (ssDNA) underlines its crucial roles during DNA replication and repair. A combination of immunofluorescence and live cell imaging of GFP-tagged RPA70 revealed that RPA, in contrast to other replication factors, does not cluster into replication foci, which is explained by its short residence time at ssDNA. In addition to replication, RPA also plays a crucial role in both the pre- and post-incision steps of nucleotide excision repair (NER).

Ubiquitin at work: the ubiquitous regulation of the damage recognition step of NER.

Nucleotide excision repair (NER) removes a wide variety of helix distorting DNA lesions. NER comprises two damage recognition sub-pathways: GG-NER operates genome wide, whereas TC-NER specifically removes transcription-blocking lesions from the transcribed strand of actively transcribed genes. NER is a multistep process, which requires the concerted action of 30 proteins that need to be tightly controlled at the right time and place for efficient repair.

RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response.

Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified.