Release of CHK-2 from PPM-1.D anchorage schedules meiotic entry.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35171669.
- Also identified by DOI 10.1126/sciadv.abl8861 and PMC identifier 8849337.
- Licence recorded as CC BY-NC.
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Abstract
Transition from the stem/progenitor cell fate to meiosis is mediated by several redundant posttranscriptional regulatory pathways in <i>Caenorhabditis elegans</i>. Interfering with all three branches causes tumorous germ lines. SCF<sup>PROM-1</sup> comprises one branch and mediates a scheduled degradation step at entry into meiosis. <i>prom-1</i> mutants show defects in the timely initiation of meiotic prophase I events, resulting in high rates of embryonic lethality. Here, we identify the phosphatase PPM-1.D/Wip1 as crucial substrate for PROM-1. We report that PPM-1.D antagonizes CHK-2 kinase, a key regulator for meiotic prophase initiation, including DNA double-strand breaks, chromosome pairing, and synaptonemal complex formation. We propose that PPM-1.D controls the amount of active CHK-2 via both catalytic and noncatalytic activities; notably, noncatalytic regulation seems to be crucial at meiotic entry. PPM-1.D sequesters CHK-2 at the nuclear periphery, and programmed SCF<sup>PROM-1</sup>-mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.