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Science ; 355(6323): 403-407, 2017 01 27.
Article in English | MEDLINE | ID: mdl-28059716

ABSTRACT

Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)-modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.


Subject(s)
Crossing Over, Genetic/physiology , Ligases/metabolism , Meiosis/physiology , Proteasome Endopeptidase Complex/metabolism , Small Ubiquitin-Related Modifier Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Cell Cycle Proteins , Chromosome Pairing , Chromosomes, Mammalian/metabolism , Crossing Over, Genetic/genetics , Ligases/genetics , Male , Meiosis/genetics , Mice , Mice, Mutant Strains , Proteolysis , Spermatocytes/cytology , Spermatocytes/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination
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