Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over

Molecular Cell
Wei HeNeil Hunter

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.

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Citations

Jul 12, 2020·Yeast·Christopher M FurmanEric Alani
Apr 14, 2021·Nature Plants·Divyashree C NageswaranIan R Henderson
May 1, 2021·Frontiers in Cell and Developmental Biology·Funda M Kar, Andreas Hochwagen
Apr 27, 2021·Frontiers in Plant Science·Jamie N OrrIsabelle Colas
May 27, 2021·Journal of Cell Science·Lexy von Diezmann, Ofer Rog
Jul 23, 2021·Current Opinion in Genetics & Development·Aurore SanchezPetr Cejka
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Nila M PazhayamJeff Sekelsky
Aug 22, 2021·Nucleic Acids Research·Ying WangLiangran Zhang

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