PgmNr M267: A SUMO-Ubiquitin Relay Recruits Proteasomes to Chromosome Axes to Regulate Meiotic Recombination.

Authors:
Neil Hunter 1 ; Prasada Rao 1 ; Huanyu Qiao 1 ; Shubhang Bhatt 1 ; Logan Bailey 1 ; Hung Tran 1 ; Sarah Bourne 1 ; Wendy Qiu 1 ; Anusha Deshpande 1 ; Ajay Sharma 1 ; Connor Beebout 1 ; Roberto Pezza 2


Institutes
1) Univ California, Davis, Davis, CA and the Howard Hughes Medical Institute; 2) Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.


Abstract:

Meiosis produces haploid gametes through a succession of chromosomal events that include pairing, synapsis and recombination. These events are highly orchestrated, but the mechanisms that regulate them are poorly understood. We demonstrate that SUMO, ubiquitin and proteasomes specifically localize along chromosome axes in mouse and mediate major events of meiotic prophase including synapsis and recombination. Axis-localized conjugation of SUMO and ubiquitin and the ensuing recruitment of proteasomes are dependent on just two E3 ligases, RNF212 and CCNB1IP1 (HEI10), previously shown to be essential for crossing over. These proteins mediate a checkpoint-like process in which RNF212-dependent SUMO conjugation stalls recombination by rendering the turnover of a subset of recombination factors dependent on CCNB1IP1-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for the regulation of crossing over via selective protein stabilization. Chromosome axes are thus revealed as hubs for regulated protein degradation via SUMO-dependent control of ubiquitin-mediated proteolysis.