Sir2 regulates stability of repetitive domains differentially in the human fungal pathogen Candida albicans.
Sir2 regulates stability of repetitive domains differentially in the human fungal pathogen Candida albicans.
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DOI：
10.1093/nar/gkw594
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发表时间：
2016-11-02
影响因子：
14.9
通讯作者：
Buscaino A
中科院分区：
文献类型：
--
作者：
Freire-Benéitez V;Gourlay S;Berman J;Buscaino A
DNA重复序列是真核生物基因组的不稳定位点，存在于核糖体DNA位点、端粒和亚端粒区域。遗传变异性和基因组稳定性之间的良好平衡调节了这些染色体区域的可塑性。这种调节机制对于利用基因组可塑性作为适应策略的微生物病原体等生物体特别重要。对于第一次，我们分析的机制，促进基因组稳定性的rDNA位点和亚端粒区在最常见的人类真菌病原体：白色念珠菌。在这种生物体中，组蛋白去乙酰化酶Sir2，异染色质的主调节因子，已经获得了调节基因组稳定性的新功能。与其他系统分析相反，C.白色念珠菌Sir2主要抑制rDNA位点的重组。我们证明，在亚端粒区域的重组是由一种新的DNA元件，TLO的重复元件，TRE，和Sir2控制。虽然TRE元件促进高水平的重组，但Sir2抑制这种重组率。最后，我们证明，在C。白念珠菌，调节基因组稳定性的机制是可塑性的，因为不同的环境应激条件导致一般基因组不稳定性并掩盖Sir2介导的亚端粒重组控制。我们的数据突出了调节基因组稳定性的机制如何在C.白色念珠菌
DNA repeats, found at the ribosomal DNA locus, telomeres and subtelomeric regions, are unstable sites of eukaryotic genomes. A fine balance between genetic variability and genomic stability tunes plasticity of these chromosomal regions. This tuning mechanism is particularly important for organisms such as microbial pathogens that utilise genome plasticity as a strategy for adaptation. For the first time, we analyse mechanisms promoting genome stability at the rDNA locus and subtelomeric regions in the most common human fungal pathogen: Candida albicans. In this organism, the histone deacetylase Sir2, the master regulator of heterochromatin, has acquired novel functions in regulating genome stability. Contrary to any other systems analysed, C. albicans Sir2 is largely dispensable for repressing recombination at the rDNA locus. We demonstrate that recombination at subtelomeric regions is controlled by a novel DNA element, the TLO Recombination Element, TRE, and by Sir2. While the TRE element promotes high levels of recombination, Sir2 represses this recombination rate. Finally, we demonstrate that, in C. albicans, mechanisms regulating genome stability are plastic as different environmental stress conditions lead to general genome instability and mask the Sir2-mediated recombination control at subtelomeres. Our data highlight how mechanisms regulating genome stability are rewired in C. albicans.
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DOI：
10.1038/nrm.2016.43
发表时间：
2016-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Lazzerini-Denchi E;Sfeir A
通讯作者：
Sfeir A
压力改变白色念珠菌中杂合性丧失的速率和类型。
影响因子：
6.4
作者：
Forche A;Abbey D;Pisithkul T;Weinzierl MA;Ringstrom T;Bruck D;Petersen K;Berman J
通讯作者：
Berman J
影响因子：
14.9
作者：
Larsen DH;Stucki M
通讯作者：
Stucki M
影响因子：
10.5
作者：
Huang, Julie;Brito, Ilana L.;Moazed, Danesh
通讯作者：
Moazed, Danesh
影响因子：
7
作者：
Jackson, Andrew P.;Gamble, John A.;Berriman, Matthew
通讯作者：
Berriman, Matthew