Yeast RAD26, a homolog of the human CSB gene, functions independently of nucleotide excision repair and base excision repair in promoting transcription through damaged bases.
RAD26 in the yeast Saccharomyces cerevisiae is the counterpart of the human Cockayne syndrome group B (CSB) gene. Both RAD26 and CSB act in the preferential repair of UV lesions on the transcribed strand, and in this process, they function together with the components of nucleotide excision repair (NER). Here, we examine the role of RAD26 in the repair of DNA lesions induced upon treatment with the alkylating agent methyl methanesulfonate (MMS). MMS-induced DNA lesions include base damages such as 3-methyl adenine and 7-methyl guanine, and these lesions are removed in yeast by the alternate competing pathways of base excision repair (BER), which is initiated by the action of MAG1-encoded N-methyl purine DNA glycosylase, and NER. Interestingly, a synergistic increase in MMS sensitivity was observed in the rad26 Delta strain upon inactivation of NER or BER, indicating that RAD26 promotes the survival of MMS-treated cells by a mechanism that acts independently of either of these repair pathways. The galactose-inducible transcription of the GAL2, GAL7, and GAL10 genes is reduced in MMS-treated rad26 Delta cells and also in mag1 Delta rad14 Delta cells, whereas a very severe reduction in transcription occurs in MMS-treated mag1 Delta rad14 Delta rad26 Delta cells. From these observations, we infer that RAD26 plays a role in promoting transcription by RNA polymerase II through damaged bases. The implications of these observations are discussed in this paper.
Lee
Sung-Keun
SK
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061,USA.
Yu
Sung-Lim
SL
Prakash
Louise
L
Prakash
Satya
S
D020029:Base Pairing; D018797:Cell Cycle Proteins; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D045643:DNA Repair Enzymes; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D000075223:Poly-ADP-Ribose Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D014158:Transcription, Genetic; D015003:Yeasts / Q000187:drug effects / Q000235:genetics*
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009153:Mutagens; D000075223:Poly-ADP-Ribose Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C088086:rad26 protein, S pombe; D008741:Methyl Methanesulfonate; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes