Direct inhibition of RNA polymerase II transcription by RECQL5.
Direct inhibition of RNA polymerase II transcription by RECQL5.
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DOI：
10.1074/jbc.m109.015750
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发表时间：
2009-08-28
期刊：
影响因子：
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通讯作者：
Svejstrup JQ
中科院分区：
文献类型：
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作者：
Aygün O;Xu X;Liu Y;Takahashi H;Kong SE;Conaway RC;Conaway JW;Svejstrup JQ
RECQ家族的DNA解旋酶对于维持从细菌到人类的基因组完整性是重要的。虽然在理解一些人RECQ解旋酶的生化作用方面取得了进展，但RECQL 5的生化作用仍然难以捉摸。我们最近报道RECQL 5与RNA聚合酶II（RNAPII）相互作用，指出该蛋白在转录中的作用。在这里，我们表明，RECQL 5抑制启动和延伸的转录测定重建高度纯化的一般转录因子和RNAPII。在相关的、活性更高的RECQL 1解旋酶或具有正常解旋酶活性但与RNAPII相互作用的能力受损的RECQL 5版本中未观察到这种抑制。事实上，RECQL 5解旋酶活性不是抑制所必需的。我们根据RECQ 5 −/−小鼠DNA重组水平升高和癌症发病率较高的事实讨论了我们的发现。
DNA helicases of the RECQ family are important for maintaining genome integrity, from bacteria to humans. Although progress has been made in understanding the biochemical role of some human RECQ helicases, that of RECQL5 remains elusive. We recently reported that RECQL5 interacts with RNA polymerase II (RNAPII), pointing to a role for the protein in transcription. Here, we show that RECQL5 inhibits both initiation and elongation in transcription assays reconstituted with highly purified general transcription factors and RNAPII. Such inhibition is not observed with the related, much more active RECQL1 helicase or with a version of RECQL5 that has normal helicase activity but is impaired in its ability to interact with RNAPII. Indeed, RECQL5 helicase activity is not required for inhibition. We discuss our findings in light of the fact that RECQ5−/− mice have elevated levels of DNA recombination and a higher incidence of cancer.