Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation.
Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation.
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DOI：
10.1093/nar/gks565
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发表时间：
2012-09-01
影响因子：
14.9
通讯作者：
Bohr VA
中科院分区：
文献类型：
--
作者：
Berquist BR;Canugovi C;Sykora P;Wilson DM 3rd;Bohr VA
Cockayne综合征（CS）是一种罕见的人类疾病，其特征是过早衰老、神经系统异常、感音神经性听力损失和恶病质性侏儒症。最近的数据确定CS蛋白作为线粒体的物理成分，我们试图确定蛋白质的合作伙伴和作用的Cockayne综合征组B（CS B）蛋白在这个细胞器。发现CSB与主要线粒体类核、DNA复制和转录蛋白TFAM的DNA结合活性发生物理相互作用并调节其活性。线粒体转录装置的组成部分（线粒体RNA聚合酶，转录因子2B和TFAM）功能上都与CSB相互作用，并刺激其双链DNA依赖的腺苷三磷酸酶活性。此外，我们发现，患者来源的CSB缺陷的细胞表现出缺陷，在有效的线粒体转录本生产和CSB特异性地促进延长的线粒体RNA聚合酶在体外。这些观察结果为CSB在维持线粒体功能中的重要性提供了强有力的证据，并认为与CS相关的病理部分是CSB在线粒体中发挥作用的直接结果。
Cockayne syndrome (CS) is a rare human disorder characterized by pathologies of premature aging, neurological abnormalities, sensorineural hearing loss and cachectic dwarfism. With recent data identifying CS proteins as physical components of mitochondria, we sought to identify protein partners and roles for Cockayne syndrome group B (CSB) protein in this organelle. CSB was found to physically interact with and modulate the DNA-binding activity of the major mitochondrial nucleoid, DNA replication and transcription protein TFAM. Components of the mitochondrial transcription apparatus (mitochondrial RNA polymerase, transcription factor 2B and TFAM) all functionally interacted with CSB and stimulated its double-stranded DNA-dependent adenosine triphosphatase activity. Moreover, we found that patient-derived CSB-deficient cells exhibited a defect in efficient mitochondrial transcript production and that CSB specifically promoted elongation by the mitochondrial RNA polymerase in vitro. These observations provide strong evidence for the importance of CSB in maintaining mitochondrial function and argue that the pathologies associated with CS are in part, a direct result of the roles that CSB plays in mitochondria.
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影响因子：
4.8
作者：
Citterio, E;Rademakers, S;Vermeulen, W
通讯作者：
Vermeulen, W
影响因子：
5.3
作者：
Citterio, E;Van Den Boom, V;Vermeulen, W
通讯作者：
Vermeulen, W
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D
影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
影响因子：
4.8
作者：
Aamann, Maria D.;Sorensen, Martin M.;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.