The proteasome factor Bag101 binds to Rad22 and suppresses homologous recombination.
The proteasome factor Bag101 binds to Rad22 and suppresses homologous recombination.
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DOI：
10.1038/srep02022
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发表时间：
2013
影响因子：
4.6
通讯作者：
Isobe, Toshiaki
中科院分区：
文献类型：
--
作者：
Saito, Yuichiro;Takeda, Jun;Okada, Masahiro;Kobayashi, Junya;Kato, Akihiro;Hirota, Kouji;Taoka, Masato;Matsumoto, Tomohiro;Komatsu, Kenshi;Isobe, Toshiaki
尽管RAD 52通过促进RAD 51取代RPA在同源重组（HR）的起始中起关键作用，但控制RAD 52的机制仍然难以捉摸。在这里，我们表明，Bag 101，蛋白酶体功能的一个因素，调节RAD 52蛋白水平和随后的HR. LC-MS/MS分析确定Bag 101结合到Rad 22，分裂酵母同源的RAD 52。Bag 101通过其过表达降低HR频率，相反，当其缺失时，HR频率增强。与此观察结果一致，Rad 22蛋白水平降低，在细胞中，即使当Rad 22转录上调bag 101过表达，这表明蛋白酶体介导的Rad 22降解的操作。事实上，Rad 22蛋白水平在蛋白酶体突变体中是稳定的。Rad 22与Bag 101的BAG结构域物理相互作用，缺乏该结构域增强HR频率。类似地，辐射暴露触发了这些蛋白质的解离，使得Rad 22稳定并能够增强HR。
Although RAD52 plays a critical role in the initiation of homologous recombination (HR) by facilitating the replacement of RPA with RAD51, the mechanism controlling RAD52 remains elusive. Here, we show that Bag101, a factor implicated in proteasome functioning, regulates RAD52 protein levels and subsequent HR. LC-MS/MS analysis identified Bag101 which binds to Rad22, the fission yeast homologue of RAD52. Bag101 reduced HR frequency through its overexpression and conversely, HR frequencies were enhanced when it was deleted. Consistent with this observation, Rad22 protein levels was reduced in cells where bag101 was overexpressed even when Rad22 transcription was up-regulated, suggesting the operation of proteasome-mediated Rad22 degradation. Indeed, Rad22 protein levels were stabilized in proteasome mutants. Rad22 physically interacted with the BAG domain of Bag101, and a lack of this domain enhanced HR frequency. Similarly, radiation exposure triggered the dissociation of these proteins so that Rad22 was stabilized and able to enhance HR.
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影响因子：
2.6
作者：
Sato, M;Dhut, S;Toda, T
通讯作者：
Toda, T
影响因子：
2.9
作者：
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影响因子：
3.5
作者：
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通讯作者：
Postow L
影响因子：
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作者：
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通讯作者：
Ely, KR
影响因子：
5.3
作者：
Hays, SL;Firmenich, AA;Berg, P
通讯作者：
Berg, P