CRL2(LRR-1) E3-ligase regulates proliferation and progression through meiosis in the Caenorhabditis elegans germline

PLoS Genet. 2013 Mar;9(3):e1003375. doi: 10.1371/journal.pgen.1003375. Epub 2013 Mar 28.


The ubiquitin-proteolytic system controls the stability of proteins in space and time. In this study, using a temperature-sensitive mutant allele of the cul-2 gene, we show that CRL2(LRR-1) (CUL-2 RING E3 ubiquitin-ligase and the Leucine Rich Repeat 1 substrate recognition subunit) acts at multiple levels to control germline development. CRL2(LRR-1) promotes germ cell proliferation by counteracting the DNA replication ATL-1 checkpoint pathway. CRL2(LRR-1) also participates in the mitotic proliferation/meiotic entry decision, presumably controlling the stability of meiotic promoting factors in the mitotic zone of the germline. Finally, CRL2(LRR-1) inhibits the first steps of meiotic prophase by targeting in mitotic germ cells degradation of the HORMA domain-containing protein HTP-3, required for loading synaptonemal complex components onto meiotic chromosomes. Given its widespread evolutionary conservation, CUL-2 may similarly regulate germline development in other organisms as well.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / cytology
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Cell Cycle / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation*
  • Cullin Proteins* / genetics
  • Cullin Proteins* / metabolism
  • DNA Replication
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Meiosis / genetics*
  • Mitosis
  • Phosphotransferases / metabolism
  • Synaptonemal Complex / metabolism


  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Cullin Proteins
  • HTP-3 protein, C elegans
  • cul-2 proteins, C elegans
  • Atl-1 protein, C elegans
  • Phosphotransferases
  • Ataxia Telangiectasia Mutated Proteins