Multiple kinases inhibit origin licensing and helicase activation to ensure reductive cell division during meiosis
- Massachusetts Institute of Technology, United States
- Columbia University Medical Center, United States
Abstract
Meiotic cells undergo a single round of DNA replication followed by two rounds of chromosome segregation (the meiotic divisions) to produce haploid gametes. Both DNA replication and chromosome segregation are similarly regulated by CDK oscillations in mitotic cells. Yet how these two events are uncoupled between the meiotic divisions is unclear. Using Saccharomyces cerevisiae, we show that meiotic cells inhibit both helicase loading and helicase activation to prevent DNA replication between the meiotic divisions. CDK and the meiosis‑specific kinase Ime2 cooperatively inhibit helicase loading, and their simultaneous inhibition allows inappropriate helicase reloading. Further analysis uncovered two previously unknown mechanisms by which Ime2 inhibits helicase loading. Finally, we show that CDK and the polo‑like kinase Cdc5 trigger degradation of Sld2, an essential helicase‑activation protein. Together, our data demonstrate that multiple kinases inhibit both helicase loading and activation between the meiotic divisions, thereby ensuring reductive cell division.
Article and author information
Author details
Funding
Howard Hughes Medical Institute (Investigator Award)
- Stephen P Bell
National Cancer Institute (Biopolymer Facility Support)
- Stephen P Bell
National Institute of General Medical Sciences (Gradaute Student Fellowship)
- David V Phizicky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Phizicky et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,696
- views
-
- 363
- downloads
-
- 22
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Multiple kinases inhibit origin licensing and helicase activation to ensure reductive cell division during meiosis
eLife 7:e33309.
https://doi.org/10.7554/eLife.33309
