The Uve1 endonuclease is regulated by the white collar complex to protect cryptococcus neoformans from UV damage.
The Uve1 endonuclease is regulated by the white collar complex to protect cryptococcus neoformans from UV damage.
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DOI：
10.1371/journal.pgen.1003769
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Idnurm A
中科院分区：
文献类型：
--
作者：
Verma S;Idnurm A
致病真菌新型隐球菌利用 Bwc1-Bwc2 光感受器复合物来调节交配，以响应光、毒力和紫外线辐射耐受性。该复合体如何控制这些功能尚不清楚。在这里，我们鉴定并表征了隐球菌中的一个基因 UVE1，该基因的突变导致紫外线过敏表型。裂殖酵母裂殖酵母中的同源基因编码在 UVDE 依赖性切除修复 (UVER) 途径中发挥作用的无嘌呤/无嘧啶核酸内切酶。 C. neoformans UVE1 补充了粟酒裂殖酵母 uvde 敲除菌株。 UVE1 在隐球菌、粗糙脉孢菌和布拉克斯利须霉菌中以 Bwc1 依赖性方式进行光调节，这两种物种代表了真菌中另外两个主要谱系。 bwc1 突变体中 UVE1 的过表达挽救了它们的紫外线敏感性表型，凝胶迁移率变化实验显示 Bwc2 与 UVE1 启动子的结合，表明 UVE1 是 Bwc1-Bwc2 复合物的直接下游靶标。 Uve1-GFP 融合定位于线粒体。 uve1 突变株中紫外线引起的线粒体损伤的修复被延迟。因此，在新型隐球菌中，UVE1是响应光而调节的关键基因，负责耐受紫外线应激以保护线粒体基因组。大多数真菌使用白领复合体（WCC）来感知光，白领复合体是光感受器和转录因子的两种蛋白质组合。 WCC 调节昼夜节律、性发育、孢子形成、新陈代谢和毒力。因此，暴露在光线下可以控制真菌对人类有益或有害的特性，具体取决于真菌的种类及其与人类的相互作用。尽管光对真菌生物学很重要，但光感应对真菌的潜在进化益处仍然是个谜。在这里，我们鉴定了一种 DNA 损伤修复核酸内切酶 Uve1，它是人类病原体新型隐球菌耐受紫外线应激所需的。 UVE1 是新型隐球菌中 WCC 的直接靶标，UVE1 同源物在另外两个主要真菌谱系（子囊菌门和毛霉菌亚门）中也受到 WCC 的调节。这三个群体的差异表明，大约十亿年来，同一个转录因子复合物一直在调节一个共同的基因，以保护真菌基因组免受光的有害影响。奇怪的是，在新型隐球菌中，Uve1 定位于线粒体并有助于线粒体 DNA 修复，这表明它在该细胞器的基因组修复中的重要性。因此，真菌中存在光感应功能，以保护它们免受有害光的侵害，并且可能对光的所有其他反应都与这种选择压力有关或者是这种选择压力的次要结果。
The pathogenic fungus Cryptococcus neoformans uses the Bwc1-Bwc2 photoreceptor complex to regulate mating in response to light, virulence and ultraviolet radiation tolerance. How the complex controls these functions is unclear. Here, we identify and characterize a gene in Cryptococcus, UVE1, whose mutation leads to a UV hypersensitive phenotype. The homologous gene in fission yeast Schizosaccharomyces pombe encodes an apurinic/apyrimidinic endonuclease acting in the UVDE-dependent excision repair (UVER) pathway. C. neoformans UVE1 complements a S. pombe uvde knockout strain. UVE1 is photoregulated in a Bwc1-dependent manner in Cryptococcus, and in Neurospora crassa and Phycomyces blakesleeanus that are species that represent two other major lineages in the fungi. Overexpression of UVE1 in bwc1 mutants rescues their UV sensitivity phenotype and gel mobility shift experiments show binding of Bwc2 to the UVE1 promoter, indicating that UVE1 is a direct downstream target for the Bwc1-Bwc2 complex. Uve1-GFP fusions localize to the mitochondria. Repair of UV-induced damage to the mitochondria is delayed in the uve1 mutant strain. Thus, in C. neoformans UVE1 is a key gene regulated in response to light that is responsible for tolerance to UV stress for protection of the mitochondrial genome. The majority of fungi sense light using the White Collar complex (WCC), a two-protein combination of a photoreceptor and a transcription factor. The WCC regulates circadian rhythms, sexual development, sporulation, metabolism, and virulence. As such, the exposure to light controls properties of fungi that are beneficial and detrimental to people, depending on the species and its interaction with humans. Despite the importance of light on fungal biology, the underlying evolutionary benefit of light-sensing in fungi has remained a mystery. Here we identify a DNA damage repair endonuclease, Uve1, required for UV stress tolerance in the human pathogen Cryptococcus neoformans. UVE1 is a direct target of the WCC in C. neoformans, and UVE1 homologs are also regulated by WCC in two other major lineages of fungi, the Ascomycota and Mucoromycotina. The divergence of the three groups indicates that for about a billion years the same transcription factor complex has regulated a common gene to protect fungal genomes from deleterious effects of light. Curiously, in C. neoformans Uve1 localizes to mitochondria and contributes to mitochondrial DNA repair, implicating its importance in genome repair of this organelle. Thus, light-sensing in fungi exists to protect them against harmful light, and likely all other responses to light relate to or are a secondary consequence of this selective pressure.
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