학술논문

A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination
Document Type
article
Source
Science. 355(6323)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
Biotechnology
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
Cell Cycle Proteins
Chromosome Pairing
Chromosomes
Mammalian
Crossing Over
Genetic
Ligases
Male
Meiosis
Mice
Mice
Mutant Strains
Proteasome Endopeptidase Complex
Proteolysis
Small Ubiquitin-Related Modifier Proteins
Spermatocytes
Ubiquitin
Ubiquitin-Protein Ligases
Ubiquitination
General Science & Technology
Language
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.