Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis
Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis
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DOI：
10.1242/jcs.042382
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发表时间：
2009-02-15
影响因子：
4
通讯作者：
Sirri, Valentina
中科院分区：
文献类型：
--
作者：
Grob, Alice;Roussel, Pascal;Sirri, Valentina
Sirtuins也被称为III类组蛋白去乙酰化酶，与细胞分裂、细胞凋亡、DNA损伤修复、基因组沉默和长寿的调控有关。据报道，核仁SIRT7 （SIRT7）参与调控核糖体基因（rDNA）的转录，但没有关于SIRT7在细胞周期中调控的数据。在这里，我们分析了内源性SIRT7在有丝分裂期间的行为，而rDNA转录受到抑制。SIRT7仍然与核仁组织者区相关，RNA聚合酶I机制也是如此。SIRT7直接与rDNA转录因子UBF相互作用。此外，SIRT7在有丝分裂期间通过CDK1-cyclin B途径磷酸化，并在有丝分裂结束时在rDNA转录开始之前被一种对冈田酸敏感的磷酸酶去磷酸化。有趣的是，在释放对rDNA转录的有丝分裂抑制之前，去磷酸化事件诱导SIRT7的羧基末端区域的构象修饰。由于SIRT7的活性是恢复末期rDNA转录所必需的，我们认为这种构象修饰调节了rDNA转录的开始。
Sirtuins, also designated class III histone deacetylases, are implicated in the regulation of cell division, apoptosis, DNA damage repair, genomic silencing and longevity. The nucleolar Sirtuin7 (SIRT7) was reported to be involved in the regulation of ribosomal gene (rDNA) transcription, but there are no data concerning the regulation of SIRT7 during the cell cycle. Here we have analyzed the behavior of endogenous SIRT7 during mitosis, while rDNA transcription is repressed. SIRT7 remains associated with nucleolar organizer regions, as does the RNA polymerase I machinery. SIRT7 directly interacts with the rDNA transcription factor UBF. Moreover, SIRT7 is phosphorylated via the CDK1-cyclin B pathway during mitosis and dephosphorylated by a phosphatase sensitive to okadaic acid at the exit from mitosis before onset of rDNA transcription. Interestingly, dephosphorylation events induce a conformational modification of the carboxy-terminal region of SIRT7 before the release of mitotic repression of rDNA transcription. As SIRT7 activity is required to resume rDNA transcription in telophase, we propose that this conformational modification regulates onset of rDNA transcription.