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 PMID:33127680  

ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers.

Debabrata Das | Shin-Yu Chen | Swathi Arur
Science advances | 2020

Oocyte numbers, a critical determinant of female reproductive fitness, are highly regulated, yet the mechanisms underlying this regulation remain largely undefined. In the Caenorhabditis elegans gonad, RAS/extracellular signal-regulated kinase (ERK) signaling regulates oocyte numbers; mechanisms are unknown. We show that the RAS/ERK pathway phosphorylates meiotic chromosome axis protein HTP-1 at serine-325 to control chromosome dynamics and regulate oocyte number. Phosphorylated HTP-1(S325) accumulates in vivo in an ERK-dependent manner in early-mid pachytene stage germ cells and is necessary for synaptonemal complex extension and/or maintenance. Lack of HTP-1 phosphorylation leads to asynapsis and persistence of meiotic double-strand breaks, causing delayed meiotic progression and reduced oocyte number. In contrast, early onset of ERK activation causes precocious meiotic progression, resulting in increased oocyte number, which is reversed by removal of HTP-1 phosphorylation. The RAS/ERK/HTP-1 signaling cascade thus functions to monitor formation and maintenance of synapsis for timely resolution of double-strand breaks, oocyte production, and reproductive fitness.

Pubmed ID: 33127680

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA016672
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM098200

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