The DNA repair protein rad23 is a negative regulator of multi-ubiquitin chain assembly.
Rad23 is a nucleotide-excision repair protein with a previously unknown biochemical function. We determined that yeast and human Rad23 inhibited multi-ubiquitin (Ub) chain formation and the degradation of proteolytic substrates. Significantly, Rad23 could be co-precipitated with a substrate that contained a short multi-Ub chain. The UV sensitivity of rad23Delta was reduced in mutants lacking the E2 enzyme Ubc4, or the multi-Ub chain-promoting factor Ufd2. These studies suggest that the stability of proteolytic substrates is governed by the competing action of multi-Ub chain-promoting and chain-inhibiting factors. The stabilization of DNA repair and stress factors could represent an important biological function of Rad23.
Ortolan
T G
TG
Department of Biochemistry, Robert Wood Johnson Medical School-UMDNJ, 675 Hoes Lane, Piscataway, New Jersey 08854, USA.
Tongaonkar
P
P
Lambertson
D
D
Chen
L
L
Schauber
C
C
Madura
K
K
D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C086985:RAD23A protein, human; D044763:Ubiquitin-Conjugating Enzymes; C063109:ubiquitin-conjugating enzyme UBC4; D008025:Ligases; C114683:UFD2 protein, S cerevisiae; D045643:DNA Repair Enzymes