RAD4

Summary

Gene Symbol: RAD4
Description: Rad4p
Alias: Rad4p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Kim I, Ahn J, Liu C, Tanabe K, Apodaca J, Suzuki T, et al. The Png1-Rad23 complex regulates glycoprotein turnover. J Cell Biol. 2006;172:211-9 pubmed
    ..We propose that the substrate specificity of Rad23 and other Ub binding proteins is determined by their interactions with various cofactors involved in specific degradation pathways. ..
  2. Xie Z, Liu S, Zhang Y, Wang Z. Roles of Rad23 protein in yeast nucleotide excision repair. Nucleic Acids Res. 2004;32:5981-90 pubmed
    ..In mammals, the complex of HR23B (Rad23 homolog) and XPC (yeast Rad4 homolog) has been suggested to function in the damage recognition step of NER...
  3. Chen L, Madura K. Centrin/Cdc31 is a novel regulator of protein degradation. Mol Cell Biol. 2008;28:1829-40 pubmed
    ..cerevisiae Rad23, and its human counterpart (hHR23), are present in a complex containing the DNA repair factor Rad4 (termed XPC, for xeroderma pigmentosum group C, in humans)...
  4. Gillette T, Yu S, Zhou Z, Waters R, Johnston S, Reed S. Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair. EMBO J. 2006;25:2529-38 pubmed
    The Rad23/Rad4 nucleotide excision repair (NER) protein complex functions at an early stage of the NER reaction, possibly promoting the recognition of damaged DNA...
  5. Guzder S, Habraken Y, Sung P, Prakash L, Prakash S. Reconstitution of yeast nucleotide excision repair with purified Rad proteins, replication protein A, and transcription factor TFIIH. J Biol Chem. 1995;270:12973-6 pubmed
    ..The Rad14 protein, the Rad4-Rad23 complex, the Rad2 nuclease, the Rad1-Rad10 nuclease, replication protein A, and the RNA polymerase II ..
  6. Suzuki T, Park H, Kwofie M, Lennarz W. Rad23 provides a link between the Png1 deglycosylating enzyme and the 26 S proteasome in yeast. J Biol Chem. 2001;276:21601-7 pubmed
    ..The Png1p-Rad23p complex was shown to be distinct from the well established DNA repair complex, Rad4p-Rad23p...
  7. Schauber C, Chen L, Tongaonkar P, Vega I, Lambertson D, Potts W, et al. Rad23 links DNA repair to the ubiquitin/proteasome pathway. Nature. 1998;391:715-8 pubmed
    ..The carboxy terminus of Rad23 binds to the Rad4 DNA repair protein and creates a link between the DNA repair and proteasome pathways...
  8. Ortolan T, Chen L, Tongaonkar P, Madura K. Rad23 stabilizes Rad4 from degradation by the Ub/proteasome pathway. Nucleic Acids Res. 2004;32:6490-500 pubmed
    Rad23 protein interacts with the nucleotide excision-repair (NER) factor Rad4, and the dimer can bind damaged DNA. Rad23 also binds ubiquitinated proteins and promotes their degradation by the proteasome...
  9. den Dulk B, van Eijk P, de Ruijter M, Brandsma J, Brouwer J. The NER protein Rad33 shows functional homology to human Centrin2 and is involved in modification of Rad4. DNA Repair (Amst). 2008;7:858-68 pubmed publisher
    In the yeast Saccharomyces cerevisiae the Rad4-Rad23 complex is implicated in the initial damage recognition of the Nucleotide Excision Repair (NER) pathway...

More Information

Publications43

  1. Min J, Pavletich N. Recognition of DNA damage by the Rad4 nucleotide excision repair protein. Nature. 2007;449:570-5 pubmed
    ..Here we present the crystal structure of the yeast XPC orthologue Rad4 bound to DNA containing a cyclobutane pyrimidine dimer (CPD) lesion...
  2. Tremblay M, Teng Y, Paquette M, Waters R, Conconi A. Complementary roles of yeast Rad4p and Rad34p in nucleotide excision repair of active and inactive rRNA gene chromatin. Mol Cell Biol. 2008;28:7504-13 pubmed publisher
    ..Here we have analyzed the roles of two members of the xeroderma pigmentosum group C family of proteins, Rad4p and Rad34p, during NER in the active and inactive rDNA...
  3. Gong F, Fahy D, Smerdon M. Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. Nat Struct Mol Biol. 2006;13:902-7 pubmed
    ..chromatin-remodeling complex in Saccharomyces cerevisiae, copurify with the NER damage-recognition heterodimer Rad4-Rad23. This interaction between SWI/SNF and Rad4-Rad23 is stimulated by UV irradiation...
  4. Wang Z, Wei S, Reed S, Wu X, Svejstrup J, Feaver W, et al. The RAD7, RAD16, and RAD23 genes of Saccharomyces cerevisiae: requirement for transcription-independent nucleotide excision repair in vitro and interactions between the gene products. Mol Cell Biol. 1997;17:635-43 pubmed
    ..Complementation studies with rad4, rad7, rad16, and rad23 mutant extracts suggest physical interactions among these proteins...
  5. Lafrance Vanasse J, Arseneault G, Cappadocia L, Legault P, Omichinski J. Structural and functional evidence that Rad4 competes with Rad2 for binding to the Tfb1 subunit of TFIIH in NER. Nucleic Acids Res. 2013;41:2736-45 pubmed publisher
    XPC/Rad4 (human/yeast) recruits transcription faction IIH (TFIIH) to the nucleotide excision repair (NER) complex through interactions with its p62/Tfb1 and XPB/Ssl2 subunits...
  6. Stingele J, Schwarz M, Bloemeke N, Wolf P, Jentsch S. A DNA-dependent protease involved in DNA-protein crosslink repair. Cell. 2014;158:327-338 pubmed publisher
    ..Thus, our data suggest that Wss1 contributes to survival of DPC-harboring cells by acting on DPCs proteolytically. We propose that DPC proteolysis enables repair of these unique lesions via downstream canonical DNA repair pathways. ..
  7. Chen L, Madura K. Degradation of specific nuclear proteins occurs in the cytoplasm in Saccharomyces cerevisiae. Genetics. 2014;197:193-7 pubmed publisher
    ..We report here that two well-characterized nuclear proteins are stabilized in nuclear export mutants in Saccharomyces cerevisiae. The requirement for nuclear export defines a new regulatory step in intracellular proteolysis...
  8. Chen X, Velmurugu Y, Zheng G, Park B, Shim Y, Kim Y, et al. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC. Nat Commun. 2015;6:5849 pubmed publisher
    ..Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA...
  9. Hryciw T, Tang M, Fontanie T, Xiao W. MMS1 protects against replication-dependent DNA damage in Saccharomyces cerevisiae. Mol Genet Genomics. 2002;266:848-57 pubmed
    ..Together these results suggest a role for an Mms1-dependent, Rad52-mediated, pathway in protecting cells against replication-dependent DNA damage. ..
  10. Guzder S, Sung P, Prakash L, Prakash S. Synergistic interaction between yeast nucleotide excision repair factors NEF2 and NEF4 in the binding of ultraviolet-damaged DNA. J Biol Chem. 1999;274:24257-62 pubmed
    Saccharomyces cerevisiae RAD4, RAD7, RAD16, and RAD23 genes function in the nucleotide excision repair (NER) of ultraviolet light (UV)-damaged DNA...
  11. Hendricks C, Razlog M, Matsuguchi T, Goyal A, Brock A, Engelward B. The S. cerevisiae Mag1 3-methyladenine DNA glycosylase modulates susceptibility to homologous recombination. DNA Repair (Amst). 2002;1:645-59 pubmed
    ..susceptibility to methylation-induced recombination, and that disruption of nucleotide excision repair (NER; rad4) in mag1 cells increases cellular susceptibility to these events...
  12. Wei S, Friedberg E. A fragment of the yeast DNA repair protein Rad4 confers toxicity to E. coli and is required for its interaction with Rad7 protein. Mutat Res. 1998;400:127-33 pubmed
    The RAD4 gene of Saccharomyces cerevisiae is required for the incision of damaged DNA during nucleotide excision repair. Plasmids carrying the wild-type RAD4 gene cannot be propagated in Escherichia coli...
  13. Mao P, Smerdon M. Yeast deubiquitinase Ubp3 interacts with the 26 S proteasome to facilitate Rad4 degradation. J Biol Chem. 2010;285:37542-50 pubmed publisher
    ..Yeast Rad4-Rad23 heterodimer is responsible for recognizing DNA damage in nucleotide excision repair (NER)...
  14. Silver H, Nissley J, Reed S, Hou Y, Johnson E. A role for SUMO in nucleotide excision repair. DNA Repair (Amst). 2011;10:1243-51 pubmed publisher
    ..has been reported previously that mutants deficient for the SUMO conjugating enzyme Ubc9 contain reduced levels of Rad4, the yeast homolog of human XPC...
  15. Velmurugu Y, Chen X, Slogoff Sevilla P, Min J, Ansari A. Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex. Proc Natl Acad Sci U S A. 2016;113:E2296-305 pubmed publisher
    ..Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that Rad4 "opens" up damaged DNA by inserting a ?-..
  16. Zhang L, Chen H, Bi X, Gong F. Detection of an altered heterochromatin structure in the absence of the nucleotide excision repair protein Rad4 in Saccharomyces cerevisiae. Cell Cycle. 2013;12:2435-42 pubmed publisher
    b>Rad4p is a DNA damage recognition protein essential for global genomic nucleotide excision repair in Saccharomyces cerevisiae. Here, we show that Rad4p binds to the heterochromatic HML locus...
  17. Fasullo M, Chen Y, Bortcosh W, Sun M, Egner P. Aflatoxin B(1)-Associated DNA Adducts Stall S Phase and Stimulate Rad51 foci in Saccharomyces cerevisiae. J Nucleic Acids. 2010;2010:456487 pubmed publisher
    ..Although rad51 and rad4 mutants are mildly sensitive to AFB(1), chronic exposure of the NER deficient rad4 cells to AFB(1) leads to ..
  18. Choi D, Min M, Kim M, Lee R, Kwon S, Bae S. Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4-nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae. J Microbiol. 2014;52:292-8 pubmed publisher
    ..Based on DNA damage sensitivities induced by 4-nitroquinoline-1-oxide (4-NQO) or cisplatin, RAD4 was found to be epistatic to HRQ1...
  19. Ju D, Xie Y. A synthetic defect in protein degradation caused by loss of Ufd4 and Rad23. Biochem Biophys Res Commun. 2006;341:648-52 pubmed
    ..Here we demonstrate that Ufd4, the E3 component of the UFD pathway, is involved in controlling the degradation of Rad4, a nucleotide excision repair protein...
  20. Böhm S, Szakal B, Herken B, Sullivan M, Mihalevic M, Kabbinavar F, et al. The Budding Yeast Ubiquitin Protease Ubp7 Is a Novel Component Involved in S Phase Progression. J Biol Chem. 2016;291:4442-52 pubmed publisher
    ..In summary, our results suggest that Ubp7 contributes to S phase progression by affecting the chromatin state at replication forks, and we propose histone H2B ubiquitination as a potential substrate of Ubp7. ..
  21. Jansen L, Verhage R, Brouwer J. Preferential binding of yeast Rad4.Rad23 complex to damaged DNA. J Biol Chem. 1998;273:33111-4 pubmed
    The yeast Rad4 and Rad23 proteins form a complex that is involved in nucleotide excision repair (NER). Their function in this process is not known yet, but genetic data suggest that they act in an early step in NER...
  22. Guzder S, Sung P, Prakash L, Prakash S. Affinity of yeast nucleotide excision repair factor 2, consisting of the Rad4 and Rad23 proteins, for ultraviolet damaged DNA. J Biol Chem. 1998;273:31541-6 pubmed
    Saccharomyces cerevisiae Rad4 and Rad23 proteins are required for the nucleotide excision repair of UV light-damaged DNA...
  23. Kong M, Liu L, Chen X, Driscoll K, Mao P, Böhm S, et al. Single-Molecule Imaging Reveals that Rad4 Employs a Dynamic DNA Damage Recognition Process. Mol Cell. 2016;64:376-387 pubmed publisher
    ..Quantum dot-labeled Rad4-Rad23 (yeast XPC-RAD23B ortholog) forms non-motile complexes or conducts a one-dimensional search via either random ..
  24. Zhang L, Jones K, Smerdon M, Gong F. Assays for chromatin remodeling during nucleotide excision repair in Saccharomyces cerevisiae. Methods. 2009;48:19-22 pubmed publisher
    ..We have used the methods described here to demonstrate that the SWI/SNF chromatin remodeling complex is involved in chromatin rearrangement during NER. ..
  25. Sarkar S, Kiely R, McHugh P. The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair. J Cell Biol. 2010;191:1061-8 pubmed publisher
    ..Moreover, Ino80 interacts with the early NER damage recognition complex Rad4-Rad23 and is recruited to chromatin by Rad4 in a UV damage-dependent manner...
  26. Zhou Z, Humphryes N, van Eijk P, Waters R, Yu S, Kraehenbuehl R, et al. UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools. Nucleic Acids Res. 2015;43:7360-70 pubmed publisher
    ..expression profiling and chromatin immunoprecipitation, we demonstrate that in the absence of DNA damage the yeast Rad4-Rad23 nucleotide excision repair complex binds to the promoters of certain DNA damage response genes including DUN1,..
  27. Kiakos K, Sato A, Asao T, McHugh P, Lee M, Hartley J. DNA sequence selective adenine alkylation, mechanism of adduct repair, and in vivo antitumor activity of the novel achiral seco-amino-cyclopropylbenz[e]indolone analogue of duocarmycin AS-I-145. Mol Cancer Ther. 2007;6:2708-18 pubmed
    ..v. or p.o. Its novel structure and in vivo activity renders AS-I-145 a new paradigm in the design of novel achiral analogues of CC-1065 and the duocarmycins. ..
  28. Poletto N, Henriques J, Bonatto D. Relationship between endoplasmic reticulum- and Golgi-associated calcium homeostasis and 4-NQO-induced DNA repair in Saccharomyces cerevisiae. Arch Microbiol. 2010;192:247-57 pubmed publisher
    ..of Golgi complex, interacts with Cod1p, which regulates Ca(2+) levels in the endoplasmic reticulum (ER), and with Rad4p, which is a nucleotide excision repair (NER) protein...
  29. Li Y, Yan J, Kim I, Liu C, Huo K, Rao H. Rad4 regulates protein turnover at a postubiquitylation step. Mol Biol Cell. 2010;21:177-85 pubmed publisher
    ..However, the mechanism underlying Rad23's function in proteolysis remains unknown. Here, we demonstrate that Rad4, a Rad23-binding protein, also regulates ubiquitylated substrate turnover...
  30. Torres Ramos C, Johnson R, Prakash L, Prakash S. Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast. Mol Cell Biol. 2000;20:3522-8 pubmed
    ..A deficiency in the repair of AP sites may contribute to the internal cancers and progressive neurodegeneration that occur in XP patients. ..
  31. Connors B, Rochelle L, Roberts A, Howard G. A Synthetic Interaction between CDC20 and RAD4 in Saccharomyces cerevisiae upon UV Irradiation. Mol Biol Int. 2014;2014:519290 pubmed publisher
    ..In Saccharomyces cerevisiae, Rad4 is involved in damage recognition during nucleotide excision repair (NER) and, in conjunction with Rad23, recruits ..
  32. Georgakopoulos T, Koutroubas G, Vakonakis I, Tzermia M, Prokova V, Voutsina A, et al. Functional analysis of the Saccharomyces cerevisiae YFR021w/YGR223c/YPL100w ORF family suggests relations to mitochondrial/peroxisomal functions and amino acid signalling pathways. Yeast. 2001;18:1155-71 pubmed
    ..We found no unique phenotype attributed to the deletion of YGR223c. However, its function interferes with the function of the other two ORFs, as revealed by the effects of double- and triple-ORF deletions. ..
  33. Rolla H, Grey M, Schmidt C, Niegemann E, Brendel M, Henriques J. Mutant pso8-1 of Saccharomyces cerevisiae, sensitive to photoactivated psoralens, UV radiation, and chemical mutagens, contains a rad6 missense mutant allele. Curr Genet. 2002;41:217-23 pubmed
    ..A constructed pso8-1 rad4-4 double mutant was super-sensitive to UVC, thus indicating a synergistic interaction of the two mutant alleles...
  34. McA Nulty M, Lippard S. The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast. Mutat Res. 1996;362:75-86 pubmed
    ..lower cytotoxicity of cisplatin in the ixr1 strain is the result of enhanced repair was investigated in rad1, rad2, rad4, rad6, rad9, rad10, rad14 and rad52 backgrounds...