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Release of CHK-2 from PPM-1.D anchorage schedules meiotic entry.

Antoine BaudrimontDimitra PaouneskouAriz MohammadRaffael LichtenbergerJoshua BlundonYumi KimMarkus HartlSebastian FalkTim SchedlVerena Jantsch
Published in: Science advances (2022)
Transition from the stem/progenitor cell fate to meiosis is mediated by several redundant posttranscriptional regulatory pathways in Caenorhabditis elegans . Interfering with all three branches causes tumorous germ lines. SCF PROM-1 comprises one branch and mediates a scheduled degradation step at entry into meiosis. prom-1 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 PROM-1 -mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.
Keyphrases
  • dna damage response
  • transcription factor
  • protein kinase
  • tyrosine kinase
  • gene expression
  • oxidative stress
  • dna damage
  • dna repair
  • circulating tumor cells