Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over.

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.

Possible Adverse Effects of Repeated Botulinum Toxin A Injections to Decrease Post-Stroke Spasticity in Adults Undergoing Rehabilitation: A Review of the Literature.

Botulinum toxin A (Botox A) is widely prescribed for the management of spasticity due to stroke, and many patients receive repeated injections because the paralyzing effect diminishes after 3 to 4 months. There are many studies that report local complications of Botox A at the injected site. However, little is known about non-local or systemic adverse events with repeated injections. The purpose of this research was to examine published data about adverse effects of repeated Botox A injections. MEDLINE, CINAHL, and PEDro databases were searched for articles that report adverse effects from Botox A injections for reduction of post-stroke spasticity in adults. Based on studies selected for review, the adverse effects from Botox A injections can be classified into local, systemic, and subclinical types. Systemic and subclinical adverse effects are not commonly reported and need further studies. Therapists and the rehabilitation team need to be aware of the potential of these risk factors that may affect the participation of patients undergoing rehabilitation, and therefore other alternatives to these injections may need to be considered.