Molecular cloning and characterization of Saccharomyces cerevisiae RAD28, the yeast homolog of the human Cockayne syndrome A (CSA) gene

Bhatia, Prakash K.; Verhage, Richard A.; Brouwer, Jaap; Friedberg, Errol C.

doi:10.1128/jb.178.20.5977-5988.1996

Cited by 52 publications

(52 citation statements)

References 62 publications

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“…An even greater loss of sensitivity compared with UV was seen for strains with deletion of RAD7 and RAD16. Deletion of RAD26 and RAD28, the S. cerevisiae homologs of the Cockayne's syndrome B and A genes, did not produce any sensitivity to cisplatin or to UV, consistent with earlier reports (42,43).…”

Section: Genes Affecting Resistance Of Yeast To Cisplatinsupporting

confidence: 79%

Genome-Wide Identification of Genes Conferring Resistance to the Anticancer Agents Cisplatin, Oxaliplatin, and Mitomycin C

et al. 2004

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Cisplatin is a crucial agent in the treatment of many solid tumors, yet many tumors have either acquired or intrinsic resistance to the drug. We have used the homozygous diploid deletion pool of Saccharomyces cerevisiae, containing 4728 strains with individual deletion of all nonessential genes, to systematically identify genes that when deleted confer sensitivity to the anticancer agents cisplatin, oxaliplatin, and mitomycin C. We found that deletions of genes involved in nucleotide excision repair, recombinational repair, postreplication repair including translesional synthesis, and DNA interstrand cross-link repair resulted in sensitivity to all three of the agents, although with some differences between the platinum drugs and mitomycin C in the spectrum of required translesional polymerases. Putative defective repair of oxidative damage (imp2⌬ strain) also resulted in sensitivity to platinum and oxaliplatin, but not to mitomycin C. Surprisingly in light of their different profiles of clinical activity, cisplatin and oxaliplatin have very similar sensitivity profiles. Finally, we identified three novel genes (PSY1-3, "platinum sensitivity") that, when deleted, demonstrate sensitivity to cisplatin and oxaliplatin, but not to mitomycin C. Our results emphasize the importance of multiple DNA repair pathways responsible for normal cellular resistance to all three of the agents. Also, the similarity of the sensitivity profiles of the platinum agents with that of the known DNA interstrand cross-linking agent mitomycin C, and the importance of the gene PSO2 known to be involved in DNA interstrand cross-link repair strongly suggests that interstrand cross-links are important toxic lesions for cisplatin and oxaliplatin, at least in yeast.

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Section: Genes Affecting Resistance Of Yeast To Cisplatinsupporting

confidence: 79%

Genome-Wide Identification of Genes Conferring Resistance to the Anticancer Agents Cisplatin, Oxaliplatin, and Mitomycin C

et al. 2004

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“…CS-A and CS-B cells are abnormally sensitive to UV radiation and lose the kinetic preference for repair of the transcribed strand of transcriptionally active genes displayed by cells from healthy individuals (45). Yeast rad26 mutants (but not rad28 mutants) are also defective in strand-specific NER (4,40,43). Additionally, rad26 mutants (but not rad28 mutants) have been shown to be deficient in the recovery of GAL10 and RNR3 mRNA synthesis following inhibition of such synthesis by exposure of yeast cells to UV radiation (28).…”

Section: Resultsmentioning

confidence: 99%

“…The yeast RAD26 and RAD28 genes are the structural (and presumed functional) homologs of the human CSB and CSA genes, respectively (4,43). Mutational inactivation of the human genes results in the hereditary disease Cockayne syndrome, which is characterized by postnatal growth, neurological defects, and photosensitivity (16).…”

Section: Resultsmentioning

confidence: 99%

Yeast RNA Polymerase II Transcription In Vitro Is Inhibited in the Presence of Nucleotide Excision Repair: Complementation of Inhibition by Holo-TFIIH and Requirement for RAD26

You

Feaver

Friedberg

1998

Molecular and Cellular Biology

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The Saccharomyces cerevisiae transcription factor IIH (TFIIH) is essential both for transcription by RNA polymerase II (RNAP II) and for nucleotide excision repair (NER) of damaged DNA. We have established cell extracts which support RNAP II transcription from the yeast CYC1 promoter or NER of transcriptionally silent damaged DNA on independent plasmid templates and substrates. When plasmid templates and substrates for both processes are simultaneously incubated with these extracts, transcription is significantly inhibited. This inhibition is strictly dependent on active NER and can be complemented with purified holo-TFIIH. These results suggest that in the presence of active NER, TFIIH is preferentially mobilized from the basal transcription machinery for use in NER. Inhibition of transcription in the presence of active NER requires the RAD26 gene, the yeast homolog of the human Cockayne syndrome group B gene (CSB).Nucleotide excision repair (NER) is a biochemically complex process by which many types of base damage are excised from the genome of living cells as oligonucleotide fragments (14). This process operates both in transcriptionally silent DNA and in DNA that is undergoing active transcription by RNA polymerase II (RNAP II) (5,15,21). A signature feature of the latter NER mode is that the transcribed strand is repaired significantly faster than the nontranscribed strand, a phenomenon referred to as strand-specific repair or transcription-coupled repair (5,15,21).In eukaryotes, NER of both transcriptionally silent and transcriptionally active DNA requires more than 20 distinct gene products (14,29,51). In the yeast Saccharomyces cerevisiae, these proteins include the seven known subunits of the RNAP II basal transcription factor core TFIIH (38), encoded by the essential genes TFB1, TFB2, TFB3, TFB4, RAD3, SSL1, and SSL2 (10,13,17). Mutants with conditional mutations in each of these genes have been shown to be defective in NER by using a cell-free system that measures repair synthesis of damaged plasmids in vitro (13, 21a, 47, 48). While core transcription factor IIH (TFIIH) is essential for NER, this seven-subunit complex is not sufficient for RNAP II transcription in a reconstituted in vitro system (36). Such a system has an additional requirement for polypeptides encoded by the KIN28 and CCL1 genes, which comprise the transcription factor TFIIK (11, 36). The association of TFIIK with core TFIIH generates a complex designated holo-TFIIH (36, 37).The requirement of core TFIIH for both NER and RNAP II transcription led to initial speculation that this requirement might explain the faster rate of NER observed in the transcribed strand relative to that of the nontranscribed strand of transcriptionally active genes. It was suggested that when transcription elongation complexes arrest at sites of base damage in the transcribed strand, TFIIH might promote rapid assembly of the NER machinery at such sites, thus facilitating strandspecific repair (14, 29, 51). However, several studies have shown that TFIIH dis...

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“…CSA-or CSB-deficient cells are very sensitive to UV, a property that allowed cloning of the human CSA and CSB genes (Troelstra et al 1992;Henning et al 1995). Based on sequence homology to the encoded proteins, yeast homologs were identified and the corresponding genes were named RAD28 and RAD26, respectively (Van Gool et al 1994;Bhatia et al 1996). CSB and Rad26 share strong sequence homology, which includes the seven conserved motifs of DNA/RNA helicases in the SNF2 subfamily.…”

Section: Tc-nermentioning

confidence: 99%

DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

2013

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DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanisms that promote eukaryotic genome stability. This review will focus on repair mechanisms that involve excision of a single strand from duplex DNA with the intact, complementary strand serving as a template to fill the resulting gap. These mechanisms are of two general types: those that remove damage from DNA and those that repair errors made during DNA synthesis. The major DNA-damage repair pathways are base excision repair and nucleotide excision repair, which, in the most simple terms, are distinguished by the extent of single-strand DNA removed together with the lesion. Mistakes made by DNA polymerases are corrected by the mismatch repair pathway, which also corrects mismatches generated when single strands of non-identical duplexes are exchanged during homologous recombination. In addition to the true repair pathways, the postreplication repair pathway allows lesions or structural aberrations that block replicative DNA polymerases to be tolerated. There are two bypass mechanisms: an error-free mechanism that involves a switch to an undamaged template for synthesis past the lesion and an error-prone mechanism that utilizes specialized translesion synthesis DNA polymerases to directly synthesize DNA across the lesion. A high level of functional redundancy exists among the pathways that deal with lesions, which minimizes the detrimental effects of endogenous and exogenous DNA damage.

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Molecular cloning and characterization of Saccharomyces cerevisiae RAD28, the yeast homolog of the human Cockayne syndrome A (CSA) gene

Cited by 52 publications

References 62 publications

Genome-Wide Identification of Genes Conferring Resistance to the Anticancer Agents Cisplatin, Oxaliplatin, and Mitomycin C

Genome-Wide Identification of Genes Conferring Resistance to the Anticancer Agents Cisplatin, Oxaliplatin, and Mitomycin C

Yeast RNA Polymerase II Transcription In Vitro Is Inhibited in the Presence of Nucleotide Excision Repair: Complementation of Inhibition by Holo-TFIIH and Requirement for RAD26

DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

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