Mms19 is a mitotic gene permitting Cdk7 to be fully active as Cdk activating kinase
| Autor: | Sofia Sousa-Guimarães, Selina Niggli, Beat Suter, Rishita Narendra Nag, Paula Vazquez-Pianzola |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyclin H Cyclin-dependent kinase 1 Biology CDK-activating kinase Cell biology 03 medical and health sciences 030104 developmental biology Cyclin-dependent kinase Transcription factor II H biology.protein Cyclin-dependent kinase 7 Molecular Biology Mitosis Metaphase Developmental Biology |
| Zdroj: | Development. |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | Mms19 encodes a cytosolic iron-sulphur assembly component. We found that Drosophila Mms19 is also essential for mitotic divisions and for the proliferation of diploid cells. Reduced Mms19 activity causes severe mitotic defects in spindle dynamics and chromosome segregation, and loss of zygotic Mms19 prevents the formation of imaginal discs. The lack of mitotic tissue in Mms19 P/P larvae can be rescued by overexpression of the Cdk-activating kinase (CAK) complex, an activator of mitotic Cdk1, suggesting that Mms19 functions in mitosis to allow CAK (Cdk7/Cyclin H/Mat1) to become fully active as a Cdk1-activating kinase. When bound to Xpd and TFIIH, the CAK subunit Cdk7 phosphorylates transcriptional targets and not cell cycle Cdks. In contrast, free CAK phosphorylates and activates Cdk1. Physical and genetic interaction studies between Mms19 and Xpd suggest that their interaction prevents Xpd from binding to the CAK complex. Xpd bound to Mms19 therefore frees CAK complexes, allowing them to phosphorylate Cdk1 and facilitating progression to metaphase. The structural basis for the competitive interaction with Xpd seems to be the binding of Mms19, core TFIIH and CAK to neighbouring or overlapping regions of Xpd. |
| Databáze: | OpenAIRE |
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