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Cooperative Action of Cdk1/cyclin B and SIRT1 Is Required for Mitotic Repression of rRNA Synthesis


In metazoans, transcription is arrested during mitosis. Previous studies have established that mitotic repression of cellular transcription is mediated by Cdk1/cyclin B-dependent phosphorylation of basal transcription factors that nucleate transcription complex formation. Repression of rDNA transcription at the onset of mitosis is brought about by inactivation of the TBP-containing transcription factor SL1 by Cdk1/cyclin B-dependent phosphorylation of the TAFI110 subunit, which impairs the interaction with UBF and the assembly of pre-initiation complexes. Here we show that hCdc14B, the phosphatase that regulates Cdk1/cyclin B activity and progression through mitosis, promotes reactivation of rDNA transcription by dephosphorylating TAFI110. In addition, the NAD+-dependent deacetylase SIRT1 becomes transiently enriched in nucleoli at the onset of mitosis. SIRT1 deacetylates TAFI68, another subunit of SL1, hypoacetylation of TAFI68 destabilizing SL1 binding to the rDNA promoter and impairing transcription complex assembly. The results reveal that modulation of SL1 activity by reversible acetylation of TAFI68 and phosphorylation of TAFI110 are key modifications that mediate oscillation of rDNA transcription during cell cycle progression.


Vyšlo v časopise: Cooperative Action of Cdk1/cyclin B and SIRT1 Is Required for Mitotic Repression of rRNA Synthesis. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005246
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005246

Souhrn

In metazoans, transcription is arrested during mitosis. Previous studies have established that mitotic repression of cellular transcription is mediated by Cdk1/cyclin B-dependent phosphorylation of basal transcription factors that nucleate transcription complex formation. Repression of rDNA transcription at the onset of mitosis is brought about by inactivation of the TBP-containing transcription factor SL1 by Cdk1/cyclin B-dependent phosphorylation of the TAFI110 subunit, which impairs the interaction with UBF and the assembly of pre-initiation complexes. Here we show that hCdc14B, the phosphatase that regulates Cdk1/cyclin B activity and progression through mitosis, promotes reactivation of rDNA transcription by dephosphorylating TAFI110. In addition, the NAD+-dependent deacetylase SIRT1 becomes transiently enriched in nucleoli at the onset of mitosis. SIRT1 deacetylates TAFI68, another subunit of SL1, hypoacetylation of TAFI68 destabilizing SL1 binding to the rDNA promoter and impairing transcription complex assembly. The results reveal that modulation of SL1 activity by reversible acetylation of TAFI68 and phosphorylation of TAFI110 are key modifications that mediate oscillation of rDNA transcription during cell cycle progression.


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