Every protagonist has a sidekick: Structural aspects of human xeroderma pigmentosum-binding proteins in nucleotide excision repair

The seven xeroderma pigmentosum proteins (XPps), XPA-XPG, coordinate the nucleotide excision repair (NER) pathway, promoting the excision of DNA lesions caused by exposition to ionizing radiation, majorly from ultraviolet light. Significant efforts are made to investigate NER since mutations in any of the seven XPps may cause the xeroderma pigmentosum and trichothiodystrophy diseases. However, these proteins collaborate with other pivotal players in all known NER steps to accurately exert their purposes. Therefore, in the old and ever-evolving field of DNA repair, it is imperative to reexamine and describe their structures to understand NER properly. This work provides an up-to-date review of the protein structural aspects of the closest partners that directly interact and influence XPps: RAD23B, CETN2, DDB1, RPA (RPA70, 32, and 14), p8 (GTF2H5), and ERCC1. Structurally and functionally vital domains, regions, and critical residues are reexamined, providing structural lessons and perspectives about these indispensable proteins in the NER and other DNA repair pathways. By gathering all data related to the major human xeroderma pigmentosum-interacting proteins, this review will aid newcomers on the subject and guide structural and functional future studies.

Automated summary

The seven xeroderma pigmentosum proteins (XPps) play essential roles in the nucleotide excision repair (NER) pathway, repairing DNA damage caused by ultraviolet light exposure. These proteins collaborate with other key players to ensure the smooth progression of NER steps. Reexamining the structures of these proteins is crucial in understanding NER accurately.