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有丝分裂过程中引起基因沉默的原因

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发布日期:2009-03-17 10:26 文章来源:丁香园
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基因转录在细胞分裂期间会停止,人们知道这一事实已超过40年了。对这一点的解释一直是:染色体凝缩限制了RNA聚合酶的活性,但对芽殖酵母所做的一项研究表明,事实并不是这样的。

真实情况是,保守磷酸酶CDC14(核仁分离和有丝分裂退出所需的一种有丝分裂调控因子)通过阻止RNA聚合酶-I(Pol- I)在分裂后期向核糖体DNA定位而引起基因沉默。

如果核糖体转录不关闭,那么转录体的存在将会阻止凝缩蛋白的加载和阻断染色体凝缩及分离。

Nature 458 , 219-222 (12 March 2009) | doi :10.1038/nature07652 ; Received 30 June 2008; Accepted 13 November 2008; Published online 21 January 2009

Cdc14 inhibits transcription by RNA polymerase I during anaphase

Andrés Clemente-Blanco 1 , María Mayán-Santos 1 , David A. Schneider 2 , Félix Machín 1 , 4 , Adam Jarmuz 1 , Herbert Tschochner 3 & Luis Aragón 1
1.  Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK
2.  Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 442 Kaul Human Genetics Building, 720 20th Street South, Birmingham, Alabama 35294, USA
3.  Institut für Biochemie, Mikrobiologie und Genetik, Universität Regensburg, Munich, Germany
4.  Present address: Unidad de Investigación, Hospital Universitario Candelaria, Carretera del Rosario, 38010 Tenerife, Spain.

Chromosome condensation and the global repression of gene transcription are features of mitosis in most eukaryotes. The logic behind this phenomenon is that chromosome condensation prevents the activity of RNA polymerases. In budding yeast, however, transcription was proposed to be continuous during mitosis . Here we show that Cdc14, a protein phosphatase required for nucleolar segregation and mitotic exit , inhibits transcription of yeast ribosomal genes (rDNA) during anaphase. The phosphatase activity of Cdc14 is required for RNA polymerase I (Pol I) inhibition in vitro and in vivo . Moreover Cdc14-dependent inhibition involves nucleolar exclusion of Pol I subunits. We demonstrate that transcription inhibition is necessary for complete chromosome disjunction, because ribosomal RNA (rRNA) transcripts block condensin binding to rDNA, and show that bypassing the role of Cdc14 in nucleolar segregation requires in vivo degradation of nascent transcripts. Our results show that transcription interferes with chromosome condensation, not the reverse. We conclude that budding yeast, like most eukaryotes, inhibit Pol I transcription before segregation as a prerequisite for chromosome condensation and faithful genome separation.

Full text :http://www.nature.com/nature/journal/v458/n7235/full/nature07652.html

Download PDF :http://www.nature.com/nature/journal/v458/n7235/pdf/nature07652.pdf

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