A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination

被引:126
|
作者
Rao, H. B. D. Prasada [1 ,2 ]
Qiao, Huanyu [1 ,2 ]
Bhatt, Shubhang K. [2 ]
Bailey, Logan R. J. [2 ]
Tran, Hung D. [2 ]
Bourne, Sarah L. [2 ]
Qiu, Wendy [2 ]
Deshpande, Anusha [2 ]
Sharma, Ajay N. [2 ]
Beebout, Connor J. [2 ]
Pezza, Roberto J. [3 ]
Hunter, Neil [1 ,2 ,4 ,5 ]
机构
[1] Univ Calif Davis, Howard Hughes Med Inst, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Microbiol & Mol Genet, Davis, CA 95616 USA
[3] Oklahoma Med Res Fdn, Cell Cycle & Canc Biol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA
[4] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA
[5] Univ Calif Davis, Dept Cell Biol & Human Anat, Davis, CA 95616 USA
关键词
LIGASE HEI10; SUMOYLATION; PROTEINS; MOLECULE; MEIOSIS; RNF212; ROLES;
D O I
10.1126/science.aaf6407
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:403 / 407
页数:5
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