4.7 Article

The Saccharomyces cerevisiae histone acetyltransferase Gcn5 has a role in the photo reactivation and nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers in the MFA2 gene

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JOURNAL OF MOLECULAR BIOLOGY
卷 316, 期 3, 页码 489-499

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ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1006/jmbi.2001.5383

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nucleotide excision repair; photoreactivation; histone acetylation

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How DNA repair enzymes or complexes gain access to chromatin is still not understood. Here, we have studied the role of the S. cerevisiae histone acetyltransferase Gcn5 in photoreactivation (PR) and nucleotide excision repair (NER) at the level of the genome, the MFA2 and RPB2 genes, and at specific nucleotides within MFA2. The deletion of GCN5 markedly reduced the PR and NER of UV-induced cyclobutane pyrimidine dimers in MFA2 but much less so in RPB2, whereas no detectable defect was seen for repair of the genome overall. In Deltagcn5, the MFA2 mRNA level is reduced by fourfold, while transcription from RPB2 is reduced only to 80%. These changes in transcription correlate with the changes in NER and PR found in the Deltagcn5 mutant. However, changes in MFA2 transcription cannot account for the decrease in NER in the non-transcribed strand and the control region of MFA2 where global genome repair (GGR) operates. We conclude that the histone acetyltransferase Gcn5 influences PR and NER at MFA2 in both its transcribed and non-transcribed DNA, yet it has little effect on these processes for most of the yeast genome. As a result, we speculate that histone acetylation allows efficient access of the repair machinery to chromosomal DNA damages either indirectly via influencing transcription or directly via modifying chromatin structure irrespective of transcription. (C) 2002 Elsevier Science Ltd.

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