UBA domains mediate protein-protein interactions between two DNA damage-inducible proteins.
The Saccharomyces cerevisiae genes RAD23 and DDI1 were identified in a screen for multicopy suppressors of the temperature-sensitivity of a mutant allele of S. cerevisiae PDS1. Pds1 is a regulator of anaphase that needs to accumulate and then be degraded by the ubiquitin-proteasome pathway at the metaphase-anaphase transition for cells to progress normally through mitosis. Both the Rad23 and Ddi1 pds1 suppression phenotypes depend on a shared motif known as a UBA domain found in a variety of proteins associated with ubiquitin metabolism. UBA domains were found to be essential for homodimerization of Rad23 and heterodimerization between Rad23 and Ddi1, but not for homodimerization of Ddi1. This observation, coupled with the findings that Rad23 and Ddi1 UBA domains bind ubiquitin and that dimerization of Rad23 blocks ubiquitin binding, suggests a possible mechanism for regulating Rad23 and Ddi1 function.
Bertolaet
B L
BL
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Clarke
D J
DJ
Wolff
M
M
Watson
M H
MH
Henze
M
M
Divita
G
G
Reed
S I
SI
D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002850:Chromatography, Gel; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013489:Suppression, Genetic / Q000235:genetics; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
D018797:Cell Cycle Proteins; C108125:DDI1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; C490846:RAD23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex