Silenced yeast chromatin is maintained by Sir2 in preference to permitting histone acetylations for efficient NER.
Silenced yeast chromatin is maintained by Sir2 in preference to permitting histone acetylations for efficient NER.
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DOI：
10.1093/nar/gkq242
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发表时间：
2010-08
影响因子：
14.9
通讯作者：
Waters R
中科院分区：
文献类型：
--
作者：
Irizar A;Yu Y;Reed SH;Louis EJ;Waters R
目前对核苷酸切除修复（NER）在染色体末端的功能知之甚少。为了检验这一点，我们将URA3基因引入酵母基因组的转录活性或抑制的亚端粒区域。这使我们能够检查紫外线（UV）诱导的环丁烷嘧啶二聚体（CPD）在两种情况下相同的序列的修复。我们发现，NER是显着更有效的非压抑的亚端粒比压抑的。在非阻遏的亚端粒，紫外线辐射刺激组蛋白H3和H4乙酰化，在酵母基因组的其他区域看到类似的方式。这些修饰的发生与Sir2组蛋白脱乙酰酶的存在无关。另一方面，在受抑制的亚端粒，修复效率低得多，紫外线辐射是无法刺激组蛋白H4或H3乙酰化在Sir2的存在下。在Sir2的情况下，检测到这两种UV诱导的修饰，导致该区域的NER效率显著增加。我们的实验表明，在酵母基因组中存在这样的情况，其中现有染色质结构的维持在与有效NER相关的染色质修饰的作用上占主导地位。
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.
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