Logo of embojLink to Publisher's site
EMBO J. 1994 Nov 15; 13(22): 5361–5369.
PMCID: PMC395493

RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6.


Transcription-coupled repair (TCR) is a universal sub-pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes. It accomplishes the preferential elimination of transcription-blocking DNA lesions and permits rapid resumption of the vital process of transcription. A defect in TCR is responsible for the rare hereditary disorder Cockayne syndrome (CS). Recently we found that mutations in the ERCC6 repair gene, encoding a putative helicase, underly the repair defect of CS complementation group B. Here we report the cloning and characterization of the Saccharomyces cerevisiae homolog of CSB/ERCC6, which we designate RAD26. A rad26 disruption mutant appears viable and grows normally, indicating that the gene does not have an essential function. In analogy with CS, preferential repair of UV-induced cyclobutane pyrimidine dimers in the transcribed strand of the active RBP2 gene is severely impaired. Surprisingly, in contrast to the human CS mutant, yeast RAD26 disruption does not induce any UV-, cisPt- or X-ray sensitivity, explaining why it was not isolated as a mutant before. Recovery of growth after UV exposure was somewhat delayed in rad26. These findings suggest that TCR in lower eukaryotes is not very important for cell survival and that the global genome repair pathway of NER is the major determinant of cellular resistance to genotoxicity.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Bang DD, Verhage R, Goosen N, Brouwer J, van de Putte P. Molecular cloning of RAD16, a gene involved in differential repair in Saccharomyces cerevisiae. Nucleic Acids Res. 1992 Aug 11;20(15):3925–3931. [PMC free article] [PubMed]
  • Bohr VA. Gene specific DNA repair. Carcinogenesis. 1991 Nov;12(11):1983–1992. [PubMed]
  • Bohr VA, Smith CA, Okumoto DS, Hanawalt PC. DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Cell. 1985 Feb;40(2):359–369. [PubMed]
  • Cairns BR, Kim YJ, Sayre MH, Laurent BC, Kornberg RD. A multisubunit complex containing the SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products isolated from yeast. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1950–1954. [PMC free article] [PubMed]
  • Corpet F. Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 1988 Nov 25;16(22):10881–10890. [PMC free article] [PubMed]
  • Delmas V, Stokes DG, Perry RP. A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2414–2418. [PMC free article] [PubMed]
  • Feaver WJ, Svejstrup JQ, Bardwell L, Bardwell AJ, Buratowski S, Gulyas KD, Donahue TF, Friedberg EC, Kornberg RD. Dual roles of a multiprotein complex from S. cerevisiae in transcription and DNA repair. Cell. 1993 Dec 31;75(7):1379–1387. [PubMed]
  • French S. Consequences of replication fork movement through transcription units in vivo. Science. 1992 Nov 20;258(5086):1362–1365. [PubMed]
  • Game JC, Mortimer RK. A genetic study of x-ray sensitive mutants in yeast. Mutat Res. 1974 Sep;24(3):281–292. [PubMed]
  • Girdham CH, Glover DM. Chromosome tangling and breakage at anaphase result from mutations in lodestar, a Drosophila gene encoding a putative nucleoside triphosphate-binding protein. Genes Dev. 1991 Oct;5(10):1786–1799. [PubMed]
  • Hanawalt PC, Donahue BA, Sweder KS. Repair and transcription. Collision or collusion? Curr Biol. 1994 Jun 1;4(6):518–521. [PubMed]
  • Higgins DR, Prakash S, Reynolds P, Polakowska R, Weber S, Prakash L. Isolation and characterization of the RAD3 gene of Saccharomyces cerevisiae and inviability of rad3 deletion mutants. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5680–5684. [PMC free article] [PubMed]
  • Hirschhorn JN, Brown SA, Clark CD, Winston F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 1992 Dec;6(12A):2288–2298. [PubMed]
  • Hoeijmakers JH. Nucleotide excision repair. II: From yeast to mammals. Trends Genet. 1993 Jun;9(6):211–217. [PubMed]
  • Huang JC, Svoboda DL, Reardon JT, Sancar A. Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3664–3668. [PMC free article] [PubMed]
  • Huang ME, Chuat JC, Galibert F. A possible yeast homolog of human active-gene-repairing helicase ERCC6+. Biochem Biophys Res Commun. 1994 May 30;201(1):310–317. [PubMed]
  • Izban MG, Luse DS. The RNA polymerase II ternary complex cleaves the nascent transcript in a 3'----5' direction in the presence of elongation factor SII. Genes Dev. 1992 Jul;6(7):1342–1356. [PubMed]
  • Hanawalt P, Mellon I. Stranded in an active gene. Curr Biol. 1993 Jan;3(1):67–69. [PubMed]
  • Kassavetis GA, Geiduschek EP. RNA polymerase marching backward. Science. 1993 Feb 12;259(5097):944–945. [PubMed]
  • Laurent BC, Treich I, Carlson M. The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation. Genes Dev. 1993 Apr;7(4):583–591. [PubMed]
  • Leadon SA, Cooper PK. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499–10503. [PMC free article] [PubMed]
  • Leadon SA, Lawrence DA. Preferential repair of DNA damage on the transcribed strand of the human metallothionein genes requires RNA polymerase II. Mutat Res. 1991 Jul;255(1):67–78. [PubMed]
  • Lehmann AR. Three complementation groups in Cockayne syndrome. Mutat Res. 1982 Dec;106(2):347–356. [PubMed]
  • Mayne LV, Lehmann AR, Waters R. Excision repair in Cockayne syndrome. Mutat Res. 1982 Nov;106(1):179–189. [PubMed]
  • Mellon I, Hanawalt PC. Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand. Nature. 1989 Nov 2;342(6245):95–98. [PubMed]
  • Mellon I, Spivak G, Hanawalt PC. Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell. 1987 Oct 23;51(2):241–249. [PubMed]
  • Muchardt C, Yaniv M. A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 1993 Nov;12(11):4279–4290. [PMC free article] [PubMed]
  • Mullenders LH, Hazekamp-van Dokkum AM, Kalle WH, Vrieling H, Zdzienicka MZ, van Zeeland AA. UV-induced photolesions, their repair and mutations. Mutat Res. 1993 May;299(3-4):271–276. [PubMed]
  • Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. 1992 Jan 1;42(1):68–84. [PubMed]
  • Oller AR, Fijalkowska IJ, Dunn RL, Schaaper RM. Transcription-repair coupling determines the strandedness of ultraviolet mutagenesis in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11036–11040. [PMC free article] [PubMed]
  • Oudshoorn P, Van Steeg H, Swinkels BW, Schoppink P, Grivell LA. Subunit II of yeast QH2:cytochrome-c oxidoreductase. Nucleotide sequence of the gene and features of the protein. Eur J Biochem. 1987 Feb 16;163(1):97–103. [PubMed]
  • Peterson CL, Dingwall A, Scott MP. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2905–2908. [PMC free article] [PubMed]
  • Prakash S, Sung P, Prakash L. DNA repair genes and proteins of Saccharomyces cerevisiae. Annu Rev Genet. 1993;27:33–70. [PubMed]
  • Price A. The repair of ionising radiation-induced damage to DNA. Semin Cancer Biol. 1993 Apr;4(2):61–71. [PubMed]
  • Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. [PubMed]
  • Reines D, Chamberlin MJ, Kane CM. Transcription elongation factor SII (TFIIS) enables RNA polymerase II to elongate through a block to transcription in a human gene in vitro. J Biol Chem. 1989 Jun 25;264(18):10799–10809. [PubMed]
  • Robbins J, Dilworth SM, Laskey RA, Dingwall C. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell. 1991 Feb 8;64(3):615–623. [PubMed]
  • Roza L, van der Wulp KJ, MacFarlane SJ, Lohman PH, Baan RA. Detection of cyclobutane thymine dimers in DNA of human cells with monoclonal antibodies raised against a thymine dimer-containing tetranucleotide. Photochem Photobiol. 1988 Nov;48(5):627–633. [PubMed]
  • Sancar A, Sancar GB. DNA repair enzymes. Annu Rev Biochem. 1988;57:29–67. [PubMed]
  • Schaeffer L, Moncollin V, Roy R, Staub A, Mezzina M, Sarasin A, Weeda G, Hoeijmakers JH, Egly JM. The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. EMBO J. 1994 May 15;13(10):2388–2392. [PMC free article] [PubMed]
  • Schaeffer L, Roy R, Humbert S, Moncollin V, Vermeulen W, Hoeijmakers JH, Chambon P, Egly JM. DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. Science. 1993 Apr 2;260(5104):58–63. [PubMed]
  • Selby CP, Sancar A. Molecular mechanism of transcription-repair coupling. Science. 1993 Apr 2;260(5104):53–58. [PubMed]
  • Selby CP, Witkin EM, Sancar A. Escherichia coli mfd mutant deficient in "mutation frequency decline" lacks strand-specific repair: in vitro complementation with purified coupling factor. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11574–11578. [PMC free article] [PubMed]
  • Smerdon MJ, Thoma F. Site-specific DNA repair at the nucleosome level in a yeast minichromosome. Cell. 1990 May 18;61(4):675–684. [PubMed]
  • Sweder KS, Hanawalt PC. Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10696–10700. [PMC free article] [PubMed]
  • Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC, Kennison JA. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992 Feb 7;68(3):561–572. [PubMed]
  • Tanaka K, Kawai K, Kumahara Y, Ikenaga M, Okada Y. Genetic complementation groups in cockayne syndrome. Somatic Cell Genet. 1981 Jul;7(4):445–455. [PubMed]
  • Troelstra C, van Gool A, de Wit J, Vermeulen W, Bootsma D, Hoeijmakers JH. ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes. Cell. 1992 Dec 11;71(6):939–953. [PubMed]
  • Van Houten B. Nucleotide excision repair in Escherichia coli. Microbiol Rev. 1990 Mar;54(1):18–51. [PMC free article] [PubMed]
  • van Hoffen A, Natarajan AT, Mayne LV, van Zeeland AA, Mullenders LH, Venema J. Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells. Nucleic Acids Res. 1993 Dec 25;21(25):5890–5895. [PMC free article] [PubMed]
  • Venema J, Mullenders LH, Natarajan AT, van Zeeland AA, Mayne LV. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707–4711. [PMC free article] [PubMed]
  • Verhage R, Zeeman AM, de Groot N, Gleig F, Bang DD, van de Putte P, Brouwer J. The RAD7 and RAD16 genes, which are essential for pyrimidine dimer removal from the silent mating type loci, are also required for repair of the nontranscribed strand of an active gene in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Sep;14(9):6135–6142. [PMC free article] [PubMed]
  • Winston F, Carlson M. Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet. 1992 Nov;8(11):387–391. [PubMed]
  • Yoshimoto H, Yamashita I. The GAM1/SNF2 gene of Saccharomyces cerevisiae encodes a highly charged nuclear protein required for transcription of the STA1 gene. Mol Gen Genet. 1991 Aug;228(1-2):270–280. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...