Xpd/Ercc2 regulates CAK activity and mitotic progression

Chen, Jian; Larochelle, Stéphane; Li, Xiaoming; Suter, Beat (2003). Xpd/Ercc2 regulates CAK activity and mitotic progression. Nature, 424(6945), pp. 228-232. Macmillan Journals Ltd. 10.1038/nature01746

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General transcription factor IIH (TFIIH) consists of nine sub- units: cyclin-dependent kinase 7 (Cdk7), cyclin H and MAT1 (forming the Cdk-activating-kinase or CAK complex), the two helicases Xpb/Hay and Xpd, and p34, p44, p52 and p62 (refs 1–3). As the kinase subunit of TFIIH, Cdk7 participates in basal transcription by phosphorylating the carboxy-terminal domain of the largest subunit of RNA polymerase II1,4,5. As part of CAK, Cdk7 also phosphorylates other Cdks, an essential step for their activation6–9. Here we show that the Drosophila TFIIH com- ponent Xpd negatively regulates the cell cycle function of Cdk7, the CAK activity. Excess Xpd titrates CAK activity, resulting in decreased Cdk T-loop phosphorylation, mitotic defects and lethality, whereas a decrease in Xpd results in increased CAK activity and cell proliferation. Moreover, Xpd is downregulated at the beginning of mitosis when Cdk1, a cell cycle target of Cdk7, is most active. Downregulation of Xpd thus seems to contribute to the upregulation of mitotic CAK activity and to regulate mitotic progression positively. Simultaneously, the downregulation of Xpd might be a major mechanism of mitotic silencing of basal transcription.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Suter, Beat

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0028-0836

Publisher:

Macmillan Journals Ltd.

Language:

English

Submitter:

Beat Suter

Date Deposited:

26 May 2015 16:07

Last Modified:

26 May 2015 16:07

Publisher DOI:

10.1038/nature01746

PubMed ID:

12853965

BORIS DOI:

10.7892/boris.68947

URI:

https://boris.unibe.ch/id/eprint/68947

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