Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1
D J Rossi1, A Londesborough, N Korsisaari
1Molecular Cancer Biology Research Program, Biomedicum Helsinki and Haartman Institute, University of Helsinki, PO Box 63, 00014 Helsinki, Finland.
The EMBO Journal
|June 2, 2001
Summary
Mat1 is essential for cell cycle progression and development in mice. Loss of Mat1 disrupts endoreduplication and RNA polymerase II C-terminal domain phosphorylation, leading to embryonic lethality.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- The Cdk7-cyclin H-Mat1 complex is a key component of the basal transcription factor TFIIH.
- This complex functions as a cyclin-dependent kinase (Cdk)-activating kinase, crucial for cell cycle regulation.
Purpose of the Study:
- To investigate the role of the murine Mat1 gene in embryonic development and cell proliferation.
- To understand the impact of Mat1 disruption on cell cycle progression and RNA polymerase II phosphorylation.
Main Methods:
- Gene disruption of the murine Mat1 gene.
- Analysis of blastocyst development and cell proliferation in vitro.
- Assessment of endoreduplication, S phase entry, and RNA polymerase II C-terminal domain (CTD) phosphorylation.
Main Results:
- Disruption of the Mat1 gene caused peri-implantation lethality in mice.
- Mat1(-/-) blastocysts developed viable trophoblast giant cells but failed to proliferate in mitotic lineages.
- Mat1(-/-) cells arrested in endoreduplication, showing an inability to enter S phase and defects in CTD phosphorylation.
Conclusions:
- Mat1 plays an essential role in endocycle progression during early embryonic development.
- While Mat1 influences CTD phosphorylation, it is not essential for RNA polymerase II-mediated transcription.
- The study highlights Mat1's critical function in cell cycle control and development.
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