Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis.
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.
Grob
Alice
A
Institut Jacques Monod, UMR 7592 CNRS/Universités Paris 6 et 7, 2 Place Jussieu, 75251 Paris Cedex 05, France.
Roussel
Pascal
P
Wright
Jane E
JE
McStay
Brian
B
Hernandez-Verdun
Danièle
D
Sirri
Valentina
V
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D019926:Cyclin B / Q000378:metabolism; D004275:DNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008938:Mitosis; D009697:Nucleolus Organizer Region / Q000201:enzymology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000378:metabolism*; D015533:Transcriptional Activation
D019926:Cyclin B; D004275:DNA, Ribosomal; D035463:Pol1 Transcription Initiation Complex Proteins; C510661:SIRT7 protein, human; C063844:transcription factor UBF; D016203:CDC2 Protein Kinase; D010744:Phosphoric Monoester Hydrolases; D037761:Sirtuins