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

The rad16 mutant of Saccharomyces cerevisiae was previously shown to be impaired in removal of UV-induced pyrimidine dimers from the silent mating-type loci (D. D. Bang, R. A. Verhage, N. Goosen, J. Brouwer, and P. van de Putte, Nucleic Acids Res. 20:3925-3931, 1992). Here we show that rad7 as well as rad7 rad16 double mutants have the same repair phenotype, indicating that the RAD7 and RAD16 gene products might operate in the same nucleotide excision repair subpathway. Dimer removal from the genome overall is essentially incomplete in these mutants, leaving about 20 to 30% of the DNA unrepaired. Repair analysis of the transcribed RPB2 gene shows that the nontranscribed strand is not repaired at all in rad7 and rad16 mutants, whereas the transcribed strand is repaired in these mutants at a fast rate similar to that in RAD+ cells. When the results obtained with the RPB2 gene can be generalized, the RAD7 and RAD16 proteins not only are essential for repair of silenced regions but also function in repair of nontranscribed strands of active genes in S. cerevisiae. The phenotype of rad7 and rad16 mutants closely resembles that of human xeroderma pigmentosum complementation group C (XP-C) cells, suggesting that RAD7 and RAD16 in S. cerevisiae function in the same pathway as the XPC gene in human cells. RAD4, which on the basis of sequence homology has been proposed to be the yeast XPC counterpart, seems to be involved in repair of both inactive and active yeast DNA, challenging the hypothesis that RAD4 and XPC are functional homologs.

[1]  R. Baan,et al.  Removal of UV-induced DNA lesions in mouse epidermis soon after irradiation. , 1994, Journal of photochemistry and photobiology. B, Biology.

[2]  K. Tanaka,et al.  Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23. , 1994, The EMBO journal.

[3]  E. Friedberg,et al.  Cloning the Drosophila homolog of the xeroderma pigmentosum complementation group C gene reveals homology between the predicted human and Drosophila polypeptides and that encoded by the yeast RAD4 gene. , 1994, Nucleic acids research.

[4]  R. Wood,et al.  Xeroderma pigmentosum and nucleotide excision repair of DNA. , 1994, Trends in biochemical sciences.

[5]  A. Bardwell,et al.  Dual roles of a multiprotein complex from S. cerevisiae in transcription and DNA repair , 1993, Cell.

[6]  L. Mullenders,et al.  Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells. , 1993, Nucleic acids research.

[7]  P. Chambon,et al.  DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. , 1993, Science.

[8]  A. Sancar,et al.  Molecular mechanism of transcription-repair coupling. , 1993, Science.

[9]  C. Downes,et al.  Fine tuning of DNA repair in transcribed genes: mechanisms, prevalence and consequences. , 1993, Bioessays.

[10]  P. Sung,et al.  DNA repair genes and proteins of Saccharomyces cerevisiae. , 1993, Annual review of genetics.

[11]  J. Hoeijmakers,et al.  ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes , 1992, Cell.

[12]  P. Hanawalt,et al.  Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Lawrence,et al.  Strand-selective repair of DNA damage in the yeast GAL7 gene requires RNA polymerase II. , 1992, The Journal of biological chemistry.

[14]  F. Winston,et al.  Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. , 1992, Trends in genetics : TIG.

[15]  P. van de Putte,et al.  Molecular cloning of RAD16, a gene involved in differential repair in Saccharomyces cerevisiae. , 1992, Nucleic acids research.

[16]  B. Dujon,et al.  The complete DNA sequence of yeast chromosome III , 1992, Nature.

[17]  L. Mullenders,et al.  Transcription affects the rate but not the extent of repair of cyclobutane pyrimidine dimers in the human adenosine deaminase gene. , 1992, The Journal of biological chemistry.

[18]  I. Herskowitz,et al.  Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription , 1992, Cell.

[19]  Ira Herskowitz,et al.  11 Mating-type Determination and Mating-type Interconversion in Saccharomyces cerevisiae , 1992 .

[20]  R. Legerski,et al.  Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C , 1992, Nature.

[21]  A. Sancar,et al.  Escherichia coli mfd mutant deficient in "mutation frequency decline" lacks strand-specific repair: in vitro complementation with purified coupling factor. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Oscar M. Aparicio,et al.  Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae , 1991, Cell.

[23]  L. Mullenders,et al.  Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes , 1991, Molecular and cellular biology.

[24]  M. Schweiger,et al.  The yeast DNA repair proteins RAD1 and RAD7 share similar putative functional domains , 1991, FEBS letters.

[25]  P. van de Putte,et al.  New insights in DNA repair: preferential repair of transcriptionally active DNA. , 1991, Mutagenesis.

[26]  Barbara L. Billington,et al.  Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription , 1990, Cell.

[27]  J. Hoeijmakers,et al.  Molecular cloning of the human DNA excision repair gene ERCC-6 , 1990, Molecular and cellular biology.

[28]  R. Poot,et al.  Differential repair of UV damage in rad mutants of Saccharomyces cerevisiae: a possible function of G2 arrest upon UV irradiation , 1990, Molecular and cellular biology.

[29]  L. Mullenders,et al.  The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Smerdon,et al.  Site-specific DNA repair at the nucleosome level in a yeast minichromosome , 1990, Cell.

[31]  P. Hanawalt,et al.  Selective repair of specific chromatin domains in UV-irradiated cells from xeroderma pigmentosum complementation group C. , 1990, Mutation research.

[32]  L. Mullenders,et al.  The residual repair capacity of xeroderma pigmentosum complementation group C fibroblasts is highly specific for transcriptionally active DNA. , 1990, Nucleic acids research.

[33]  P. Hanawalt,et al.  Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand , 1989, Nature.

[34]  P. van de Putte,et al.  Differential repair of UV damage in Saccharomyces cerevisiae. , 1989, Nucleic acids research.

[35]  E. Friedberg,et al.  Nucleotide sequence of the wild-type RAD4 gene of Saccharomyces cerevisiae and characterization of mutant rad4 alleles , 1989, Journal of bacteriology.

[36]  R. Baan,et al.  DETECTION OF CYCLOBUTANE THYMINE DIMERS IN DNA OF HUMAN CELLS WITH MONOCLONAL ANTIBODIES RAISED AGAINST A THYMINE DIMER‐ CONTAINING TETRANUCLEOTIDE , 1988, Photochemistry and photobiology.

[37]  E. Friedberg.  Deoxyribonucleic acid repair in the yeast Saccharomyces cerevisiae. , 1988, Microbiological reviews.

[38]  P. Hanawalt,et al.  Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene , 1987, Cell.

[39]  S. Prakash,et al.  RAD7 gene of Saccharomyces cerevisiae: transcripts, nucleotide sequence analysis, and functional relationship between the RAD7 and RAD23 gene products. , 1986, Molecular and cellular biology.

[40]  P. Hanawalt,et al.  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 , 1985, Cell.

[41]  R. Baan,et al.  Immunochemical quantitation of adducts induced in DNA by cis-diamminedichloroplatinum (II) and analysis of adduct-related DNA-unwinding. , 1985, Chemico-Biological Interactions.

[42]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[43]  K. Nasmyth.  The regulation of yeast mating-type chromatin structure by SIR: An action at a distance affecting both transcription and transposition , 1982, Cell.

[44]  M. Olson,et al.  Physical analysis of the CYC1-sup4 interval in Saccharomyces cerevisiae , 1981, Molecular and cellular biology.

[45]  G. Fink,et al.  Methods in yeast genetics , 1979 .