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bioRxiv · 10.1101/2021.08.02.453806

The CHK-2 antagonizing phosphatase PPM-1.D regulates meiotic entry via catalytic and non-catalytic activities

Baudrimont, A.·Paouneskou, D.·Mohammad, A.·Lichtenberger, R.·Blundon, J.·Kim, Y.·Hartl, M.·Falk, S.·Schedl, T.·Jantsch, V.
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Abstract

The transition from the stem cell/progenitor fate to meiosis is mediated by several redundant post-transcriptional regulatory pathways in C. elegans. Interfering with all three branches causes tumorous germlines. SCFPROM-1 comprises one branch and mediates a scheduled degradation step at entry into meiosis. prom-1 mutants show defects in timely initiation of events of meiotic prophase I, 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 e.g., DNA double strand breaks, chromosome pairing and synaptonemal complex formation. We propose that PPM-1.D controls the amount of active CHK-2 by both catalytic and non-catalytic activities, where strikingly the non-catalytic regulation seems to be crucial at meiotic entry. PPM-1.D sequesters CHK-2 at the nuclear periphery and programmed SCFPROM-1 mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.

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Baudrimont, A., Paouneskou, D., Mohammad, A., Lichtenberger, R., Blundon, J., Kim, Y., Hartl, M., Falk, S., Schedl, T., Jantsch, V.. 2021-08-02. The CHK-2 antagonizing phosphatase PPM-1.D regulates meiotic entry via catalytic and non-catalytic activities. https://doi.org/10.1101/2021.08.02.453806

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