Mardo Kõivomägi seminar Localized phosphorylation of RNA Polymerase II by G1 cyclin-Cdk promotes cell cycle entry | Tartu Ülikooli tehnoloogiainstituut

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Mardo Kõivomägi seminar Localized phosphorylation of RNA Polymerase II by G1 cyclin-Cdk promotes cell cycle entry

Kuupäev: 
11.10.2019 - 11:00

Localized phosphorylation of RNA Polymerase II by G1 cyclin-Cdk promotes cell cycle entry

Mardo Kõivomägi, PhD
Department of Biology, Stanford University

In the prevailing model of eukaryotic cell-cycle regulation, upstream cyclin-dependent kinase complexes inactivate the transcriptional inhibitors of G1/S genes to promote cell-cycle entry. In budding yeast, Cln3-Cdk1 is thought to phosphorylate and inactivate the transcriptional inhibitor Whi5, thereby activating the SBF transcription factor and committing cells to division. However, Whi5 phosphorylation by Cln3-Cdk1 has only been indirectly inferred and we found that Cln3-Cdk1 is not responsible for any detectable Whi5 phosphorylation in vivo. Furthermore, the presence of Cln3 at SBF-regulated promoters does not depend on Whi5. We performed an in vitro screen for Cln3-Cdk1 targets and found the RNA Polymerase II subunit Rpb1’s C-terminal unstructured region (CTD). Cln3-Cdk1 specifically phosphorylates the S5 residue in the Rpb1 CTD’s 26 YSPTSPS heptapeptide repeats. This data led us to hypothesize that Cln3-Cdk1 plays a role similar to that of the known S5 CTD kinase Ccl1-Kin28 (Cdk7), but only at specific SBF-regulated promoters. To test this, we synthetically recruited the canonical S5 kinase Ccl1-Kin28 to the Swi6 subunit of SBF, which was sufficient to restore a wild type cell cycle in cln3∆ cells. These results suggest that Cln3-Cdk1 promotes the first step in the cell cycle by phosphorylating RNA Polymerase II at SBF-regulated promoters to drive transcriptional activation of these genes. That Cln3-Cdk1 uses the same CTD phosphorylation mechanism as a large class of distantly related transcriptional Cdks undermines the distinction between cell cycle and transcriptional Cdks and illuminates an ancient and intimate relationship between the control of transcription and cell division across eukaryotes.

Place and time: Institute of Chemistry, Ravila 14a-1104, 11th of October 2019 at 11 a.m.

Korraldaja: 
Mart Loog
Kontakti e-post: 
mart.loog@ut.ee
Toimumiskoht: 
Ravila 14a-1104
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