The ubiquitin receptor Rad23: at the crossroads of nucleotide excision repair and proteasomal degradation.
A protein that exemplifies the intimate link between the ubiquitin/proteasome system (UPS) and DNA repair is the yeast nucleotide excision repair (NER) protein Rad23 and its human orthologs hHR23A and hHR23B. Rad23, which was originally identified as an important factor involved in the recognition of DNA lesions, also plays a central role in targeting ubiquitylated proteins for proteasomal degradation, an activity that it shares with other ubiquitin receptors like Dsk2 and Ddi1. Although the finding that Rad23 serves as a ubiquitin receptor explains to a large extent its importance in proteasomal degradation, the precise mode of action of Rad23 in NER and the possible link with the UPS is less clear. In this review, we discuss our present knowledge on the functions of Rad23 in protein degradation and DNA repair and speculate on the importance of the dual roles of Rad23 for the cell's ability to cope with stress conditions.
Dantuma
Nico P
NP
Department of Cell and Molecular Biology, The Medical Nobel Institute, Karolinska Institutet, Von Eulers väg 3, S-17177 Stockholm, Sweden. nico.dantuma@ki.se
Heinen
Christian
C
Hoogstraten
Deborah
D
D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology; D013312:Stress, Physiological; D054875:Ubiquitination; D014452:Ubiquitins / Q000737:chemistry / Q000502:physiology
D018797:Cell Cycle Proteins; C108125:DDI1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C100415:DSK2 protein, S cerevisiae; D005656:Fungal Proteins; C513287:RAD23B protein, human; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C086985:RAD23A protein, human; D004247:DNA; D046988:Proteasome Endopeptidase Complex; D045643:DNA Repair Enzymes