Mechanism of Start Site Selection by RNA Polymerase II INTERPLAY BETWEEN TFIIB AND Ssl2/XPB HELICASE SUBUNIT OF TFIIH
Mechanism of Start Site Selection by RNA Polymerase II INTERPLAY BETWEEN TFIIB AND Ssl2/XPB HELICASE SUBUNIT OF TFIIH
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DOI：
10.1074/jbc.m111.281576
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发表时间：
2012-01-02
影响因子：
4.8
通讯作者：
Hampsey, Michael
中科院分区：
文献类型：
--
作者：
Goel, Shivani;Krishnamurthy, Shankarling;Hampsey, Michael
TFIIB对于RNA聚合酶II的转录起始是必需的。TFIIB还与终止子区域交联，并且是以转录依赖性方式并置启动子-终止子元件的基因环所需的。酿酒酵母sua 7 -1突变编码TFIIB（E62 K）的改变形式，其对于起始位点选择和基因成环都是有缺陷的。在这里，我们报告的ssl 2突变体的分离，编码TFIIH的改变形式，作为sua 7 -1突变的冷敏感性生长缺陷的抑制剂。Ssl 2（Rad 25）是人XPB的邻位序列，并且是ATP依赖性DNA解旋酶的SF 2家族的成员。ssl 2抑制等位基因编码位于含DEVH的解旋酶结构域内的保守组氨酸残基（H508 R）的精氨酸置换。除了抑制TFIIB E62 K生长缺陷之外，Ssl 2 H508 R部分恢复正常起始位点选择和基因成环。此外，Ssl 2，像TFIIB一样，与启动子和终止子区域缔合，并且TFIIB E62 K与PMA 1终止子的减弱的缔合通过Ssl 2 H508 R抑制子恢复。这些结果定义了TFIIB和Ssl 2之间影响起始位点选择和基因成环的新的功能性相互作用。
TFIIB is essential for transcription initiation by RNA polymerase II. TFIIB also cross-links to terminator regions and is required for gene loops that juxtapose promoter-terminator elements in a transcription-dependent manner. The Saccharomyces cerevisiae sua7-1 mutation encodes an altered form of TFIIB (E62K) that is defective for both start site selection and gene looping. Here we report the isolation of an ssl2 mutant, encoding an altered form of TFIIH, as a suppressor of the cold-sensitive growth defect of the sua7-1 mutation. Ssl2 (Rad25) is orthologous to human XPB and is a member of the SF2 family of ATP-dependent DNA helicases. The ssl2 suppressor allele encodes an arginine replacement of the conserved histidine residue (H508R) located within the DEVH-containing helicase domain. In addition to suppressing the TFIIB E62K growth defect, Ssl2 H508R partially restores both normal start site selection and gene looping. Moreover, Ssl2, like TFIIB, associates with promoter and terminator regions, and the diminished association of TFIIB E62K with the PMA1 terminator is restored by the Ssl2 H508R suppressor. These results define a novel, functional interaction between TFIIB and Ssl2 that affects start site selection and gene looping.