Two mammalian homologs of yeast Rad23, HR23A and HR23B, as multifunctional proteins

Mammalian cells express two homologs of yeast Rad23, the so-called homolog of Rad23 (HR23) proteins. The HR23 proteins were identified more than two decades ago as factors involved in initiation of global genome nucleotide excision repair (GG-NER) along with their interacting partner, xeroderma pigmentosum group C (XPC) protein. Because the HR23 genes encode proteins harboring ubiquitin-like (UBL) domains at their N-termini and two ubiquitin-associated (UBA) domains in their central- and C-terminal regions, the link between HR23 proteins and proteolytic degradation has been widely explored by several methods, including yeast two-hybrid screening and co-affinity purification. To date, various HR23 protein partners have been identified, and these proteins are involved not only in DNA repair, but also in ubiquitin-dependent protein degradation, transcriptional regulation, and cell cycle control. In addition, establishment of mouse strains lacking the HR23 genes and RNA silencing of these genes in human cells demonstrated their significance in animal development and cell growth. Through these studies, the functional differences between the two HR23 proteins have been gradually revealed. Furthermore, recent comprehensive proteomic analyses will help to elucidate the functional protein-protein networks involving the HR23 proteins. •There are two mammalian homologs of yeast Rad23, HR23A and HR23B.•Both HR23A and HR23B work on nucleotide excision repair along with XPC protein.•HR23A and HR23B play distinct roles in cell proliferation, apoptosis, tumorigenesis etc.