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Updated: Aug 21, 2026
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress
Shamima Akhter1, Christopher T Richie, Jian Min Deng
1University of Texas M. D. Anderson Cancer Center, Department of Molecular Genetics, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Abstract:
Spindle poisons represent an important class of anticancer drugs that act by interfering with microtubule polymerization and dynamics and thereby induce mitotic checkpoints and apoptosis. Here we show that mammalian SNM1 functions in an early mitotic stress checkpoint that is distinct from the well-characterized spindle checkpoint that regulates the metaphase-to-anaphase transition. Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability. In addition, we show that both Snm1 and 53BP1, previously shown to interact, coimmunoprecipitate with components of the anaphase-promoting complex (APC)/cyclosome. These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation.
Insights
Mammalian SNM1 is crucial for an early mitotic stress checkpoint, distinct from the spindle checkpoint. SNM1 deficiency in cells disrupts mitosis, leading to genomic instability and reduced viability when exposed to spindle poisons.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Spindle poisons are key anticancer drugs targeting microtubule dynamics.
- Mitotic checkpoints are essential for preventing genomic instability.
Purpose of the Study:
- To investigate the role of mammalian SNM1 in mitotic stress response.
- To determine if SNM1 functions in a novel mitotic checkpoint.
Main Methods:
- Utilized Snm1-deficient mouse embryonic fibroblasts.
- Exposed cells to spindle poisons and analyzed mitotic progression.
- Performed co-immunoprecipitation assays with APC/cyclosome components.
Main Results:
- Snm1 deficiency caused increased micronuclei and failed mitotic arrest before chromosome condensation.
- Cells lacking SNM1 showed decreased mitotic delay and viability.
- SNM1 and 53BP1 co-immunoprecipitated with anaphase-promoting complex (APC)/cyclosome components.
Conclusions:
- Mammalian SNM1 is a component of an early mitotic stress checkpoint.
- This checkpoint is distinct from the spindle assembly checkpoint.
- SNM1 appears to negatively regulate the APC/cyclosome prior to chromosome condensation.
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