In mitosis, the Greatwall kinase (called microtubule-associated serine/threonine kinase like [Mastl] in mammals) is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes resume meiosis I and reach metaphase I normally but that the onset and completion of anaphase I are delayed. Moreover, after the completion of meiosis I, Mastl-null oocytes failed to enter meiosis II (MII) because they reassembled a nuclear structure containing decondensed chromatin. Our results show that Mastl is required for the timely activation of anaphase-promoting complex/cyclosome to allow meiosis I exit and for the rapid rise of Cdk1 activity that is needed for the entry into MII in mouse oocytes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178961 | PMC |
http://dx.doi.org/10.1083/jcb.201406033 | DOI Listing |
Open Biol
June 2024
Department of Genetics, University of Cambridge, Downing Street , Cambridge, UK.
The transition from oocyte to embryo requires translation of maternally provided transcripts that in is activated by Pan Gu kinase to release a rapid succession of 13 mitotic cycles. Mitotic entry is promoted by several protein kinases that include Greatwall/Mastl, whose Endosulfine substrates antagonize Protein Phosphatase 2A (PP2A), facilitating mitotic Cyclin-dependent kinase 1/Cyclin B kinase activity. Here we show that hyperactive can not only be suppressed by mutants in its Endos substrate but also by mutants in Pan Gu kinase subunits.
View Article and Find Full Text PDFElife
September 2023
Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States.
Checkpoint activation after DNA damage causes a transient cell cycle arrest by suppressing cyclin-dependent kinases (CDKs). However, it remains largely elusive how cell cycle recovery is initiated after DNA damage. In this study, we discovered the upregulated protein level of MASTL kinase hours after DNA damage.
View Article and Find Full Text PDFbioRxiv
May 2023
Department of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska, USA.
Checkpoint activation after DNA damage causes a transient cell cycle arrest by suppressing CDKs. However, it remains largely elusive how cell cycle recovery is initiated after DNA damage. In this study, we discovered the upregulated protein level of MASTL kinase hours after DNA damage.
View Article and Find Full Text PDFJ Biomol Struct Dyn
October 2022
Izmir Biomedicine and Genome Center, Izmir, Turkey.
Mastl is a mitotic kinase that is essential for error-free chromosome segregation. It is an atypical member of AGC kinase family, possessing a unique non-conserved middle region. The mechanism of Mastl activation has been studied extensively .
View Article and Find Full Text PDFEMBO J
June 2020
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes, but their specialised functions in mitosis are incompletely understood. Using degron tags for rapid inducible protein removal, we analyse how acute depletion of these proteins affects mitosis. Loss of cyclin A in G2-phase prevents mitotic entry.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!