Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1

Derrick J. Rossi, Anou Londesborough, Nina Korsisaari, Arno Pihlak, Eero Lehtonen, Mark Henkemeyer, Tomi P. Mäkelä

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The trimeric Cdk7-cyclin H-Mat1 complex comprises the kinase subunit of basal transcription factor TFIIH and has been shown to function as a cyclin-dependent kinase (Cdk)-activating kinase. Herein we report that disruption of the murine Mat1 gene leads to periimplantation lethality coincident with depletion of maternal Mat1 protein. In culture, Mat1-/- blastocysts gave rise to viable post-mitotic trophoblast giant cells while mitotic lineages failed to proliferate and survive. In contrast to wild-type trophoblast giant cells, Mat1-/- cells exhibited a rapid arrest in endoreduplication, which was characterized by an inability to enter S phase. Additionally, Mat1-/- cells exhibited defects in phosphorylation of the C-terminal domain (CTD) of RNA polymerase II on both Ser5 and Ser2 of the heptapeptide repeat. Despite this, Mat1-/- cells demonstrated apparent transcriptional and translational integrity. These data indicate an essential role for Mat1 in progression through the endocycle and suggest that while Mat1 modulates CTD phosphorylation, it does not appear to be essential for RNA polymerase II-mediated transcription.

Original languageEnglish (US)
Pages (from-to)2844-2856
Number of pages13
JournalEMBO Journal
Volume20
Issue number11
DOIs
StatePublished - Jun 1 2001

Fingerprint

RNA Polymerase III
Phosphorylation
RNA Polymerase II
S Phase
Cyclin H
Transcription Factor TFIIH
Trophoblasts
Giant Cells
Transcription
Endoreduplication
Phosphotransferases
Genes
Blastocyst
Defects
Mothers
Proteins
cyclin-dependent kinase-activating kinase

Keywords

  • Cak
  • CTD phosphorylation
  • Endoreduplication
  • Mat1
  • RNA polymerase II

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Rossi, D. J., Londesborough, A., Korsisaari, N., Pihlak, A., Lehtonen, E., Henkemeyer, M., & Mäkelä, T. P. (2001). Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1. EMBO Journal, 20(11), 2844-2856. https://doi.org/10.1093/emboj/20.11.2844

Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1. / Rossi, Derrick J.; Londesborough, Anou; Korsisaari, Nina; Pihlak, Arno; Lehtonen, Eero; Henkemeyer, Mark; Mäkelä, Tomi P.

In: EMBO Journal, Vol. 20, No. 11, 01.06.2001, p. 2844-2856.

Research output: Contribution to journalArticle

Rossi, DJ, Londesborough, A, Korsisaari, N, Pihlak, A, Lehtonen, E, Henkemeyer, M & Mäkelä, TP 2001, 'Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1', EMBO Journal, vol. 20, no. 11, pp. 2844-2856. https://doi.org/10.1093/emboj/20.11.2844
Rossi, Derrick J. ; Londesborough, Anou ; Korsisaari, Nina ; Pihlak, Arno ; Lehtonen, Eero ; Henkemeyer, Mark ; Mäkelä, Tomi P. / Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1. In: EMBO Journal. 2001 ; Vol. 20, No. 11. pp. 2844-2856.
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