Abstract:
:Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targeting proteasomal degradation. Activation of MutSγ requires the Dbf4-dependent kinase Cdc7 (DDK), which directly phosphorylates and thereby neutralizes the Msh4 degron. Genetic requirements for Msh4 phosphorylation indicate that DDK targets MutSγ only after it has bound to nascent joint molecules (JMs) in the context of synapsing chromosomes. Overexpression studies confirm that the steady-state level of Msh4, not phosphorylation per se, is the critical determinant for crossing over. At the DNA level, Msh4 phosphorylation enables the formation and crossover-biased resolution of double-Holliday Junction intermediates. Our study establishes regulated protein degradation as a fundamental mechanism underlying meiotic crossing over.
journal_name
Mol Celljournal_title
Molecular cellauthors
He W,Rao HBDP,Tang S,Bhagwat N,Kulkarni DS,Ma Y,Chang MAW,Hall C,Bragg JW,Manasca HS,Baker C,Verhees GF,Ranjha L,Chen X,Hollingsworth NM,Cejka P,Hunter Ndoi
10.1016/j.molcel.2020.02.001subject
Has Abstractpub_date
2020-04-02 00:00:00pages
168-183.e5issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(20)30071-Xjournal_volume
78pub_type
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