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

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

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Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.


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.

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