SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination

Nucleic Acids Res. 2022 May 20;50(9):5129-5144. doi: 10.1093/nar/gkac304.


Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • DNA
  • DNA Breaks, Double-Stranded*
  • Female
  • HEK293 Cells
  • Homologous Recombination
  • Humans
  • Male
  • Meiosis / genetics
  • SKP Cullin F-Box Protein Ligases* / genetics
  • Transcription Factors / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitins / genetics


  • Cell Cycle Proteins
  • FBXO47 protein, human
  • Transcription Factors
  • Ubiquitins
  • DNA
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases