Distinct regions of ATF/CREB proteins Atf1 and Pcr1 control recombination hotspot ade6-M26 and the osmotic stress response.
Distinct regions of ATF/CREB proteins Atf1 and Pcr1 control recombination hotspot ade6-M26 and the osmotic stress response.
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DOI：
10.1093/nar/gkn037
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发表时间：
2008-05
影响因子：
14.9
通讯作者：
Wahls WP
中科院分区：
文献类型：
--
作者：
Gao J;Davidson MK;Wahls WP
裂糖酵母（Schizosaccharomyces pombe）的Atf1蛋白含有ATF/CREB蛋白特有的bZIP （dna结合/蛋白二聚化）结构域，但没有其他功能结构域或明确的同源物报道。含有atf1的bZIP蛋白二聚体与crea样DNA位点结合，调节多种应激反应，并激活ade6-M26等热点的减数分裂重组。我们系统地定义了Atf1及其异源二聚体伴侣Pcr1的组织，这是Atf1依赖功能子集所必需的。令人惊讶的是，热点活性只需要Pcr1的bZIP结构域，而在没有bZIP结构域和Pcr1蛋白的情况下，Atf1与ade6的拴系促进了重组。因此，Atf1-Pcr1异源二聚体的重组激活结构域仅存在于Atf1中，而Pcr1在体内具有dna结合位点特异性。Atf1具有模块化组织，其中不同的区域对渗透胁迫反应（OSA）和减数分裂重组（HRA， HRR）有不同的影响。HRA和HRR区域分别是激活和抑制重组的必要条件和充分条件。此外，Atf1定义了一个在功能域（OSA， HRA， HRR, bZIP）中具有离散序列基序的保守蛋白家族。这些发现揭示了Atf1和Pcr1的功能组织，并阐明了bZIP蛋白可以调节多种看似不同的活性的几种机制。
The Atf1 protein of Schizosaccharomyces pombe contains a bZIP (DNA-binding/protein dimerization) domain characteristic of ATF/CREB proteins, but no other functional domains or clear homologs have been reported. Atf1-containing, bZIP protein dimers bind to CRE-like DNA sites, regulate numerous stress responses, and activate meiotic recombination at hotspots like ade6–M26. We defined systematically the organization of Atf1 and its heterodimer partner Pcr1, which is required for a subset of Atf1-dependent functions. Surprisingly, only the bZIP domain of Pcr1 is required for hotspot activity and tethering of Atf1 to ade6 promotes recombination in the absence of its bZIP domain and the Pcr1 protein. Therefore the recombination–activation domain of Atf1-Pcr1 heterodimer resides exclusively in Atf1, and Pcr1 confers DNA-binding site specificity in vivo. Atf1 has a modular organization in which distinct regions affect differentially the osmotic stress response (OSA) and meiotic recombination (HRA, HRR). The HRA and HRR regions are necessary and sufficient to activate and repress recombination, respectively. Moreover, Atf1 defines a family of conserved proteins with discrete sequence motifs in the functional domains (OSA, HRA, HRR, bZIP). These findings reveal the functional organization of Atf1 and Pcr1, and illustrate several mechanisms by which bZIP proteins can regulate multiple, seemingly disparate activities.
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