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Silenced yeast chromatin is maintained by Sir2 in preference to permitting histone acetylations for efficient NER

Author:
Irizar, Agurtzane, Yu, Yachuan, Reed, Simon H., Louis, Edward J., Waters, Raymond
Source:
Nucleic acids research 2010 v.38 no.14 pp. 4675-4686
ISSN:
0305-1048
Subject:
DNA repair, acetylation, chromatin, genes, histone deacetylase, histones, nucleic acids, transcription (genetics), ultraviolet radiation, yeasts
Abstract:
Very little is currently known about how nucleotide excision repair (NER) functions at the ends of chromosomes. To examine this, we introduced the URA3 gene into either transcriptionally active or repressed subtelomeric regions of the yeast genome. This enabled us to examine the repair of ultraviolet (UV)-induced cyclobutane pyrimidine dimers (CPDs) in identical sequences under both circumstances. We found that NER is significantly more efficient in the non-repressed subtelomere than the repressed one. At the non-repressed subtelomere, UV radiation stimulates both histones H3 and H4 acetylation in a similar fashion to that seen at other regions of the yeast genome. These modifications occur regardless of the presence of the Sir2 histone deacetylase. On the other hand, at the repressed subtelomere, where repair is much less efficient, UV radiation is unable to stimulate histone H4 or H3 acetylation in the presence of Sir2. In the absence of Sir2 both of these UV-induced modifications are detected, resulting in a significant increase in NER efficiency in the region. Our experiments reveal that there are instances in the yeast genome where the maintenance of the existing chromatin structures dominates over the action of chromatin modifications associated with efficient NER.
Agid:
2272322