Pre-RC Protein MCM7 depletion promotes mitotic exit by Inhibiting CDK1 activity
Dianpeng Zheng1, Sichao Ye1, Xiuyun Wang1
1Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
MCM7, a subunit of mini-chromosome maintenance proteins (MCM) complex, plays an important role in initiating DNA replication during the G1 phase and extending DNA strands during the S phase. Here, we demonstrated that MCM7 is not only sustained but maintains association with chromatin during M phase. Remarkably, MCM7 siRNA can accelerate mitotic exit. MCM7 depletion leads to CDK1 inactivation and promotes subsequent cohesin/RAD21 cleavage, which eventually leads to sister chromatin segregation. Moreover, MCM7 is co-localized with tubulin in the mitotic cells and MCM7 depletion results in aberrant mitosis. Our results indicate that MCM7 may exert certain functions on spindle formation to prevent cytokinesis during early mitosis by regulating CDK1 activity.
Insights
Mini-chromosome maintenance protein 7 (MCM7) associates with chromatin during M phase, and its depletion accelerates mitotic exit by regulating CDK1 activity and promoting sister chromatid segregation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mini-chromosome maintenance (MCM) proteins are essential for DNA replication initiation and elongation.
- MCM7 is a core subunit of the MCM complex, crucial for cell cycle progression.
Purpose of the Study:
- To investigate the role of MCM7 beyond DNA replication, specifically during mitosis.
- To elucidate the function of MCM7 in regulating mitotic exit and cell division.
Main Methods:
- RNA interference (siRNA) to deplete MCM7 expression.
- Western blotting to assess protein levels and activity (e.g., CDK1, RAD21).
- Immunofluorescence microscopy to examine MCM7 localization and mitotic phenotypes (e.g., spindle formation, cytokinesis).
Main Results:
- MCM7 remains associated with chromatin throughout M phase.
- MCM7 depletion accelerates mitotic exit, leading to CDK1 inactivation.
- Loss of MCM7 promotes cohesin/RAD21 cleavage, resulting in premature sister chromatid segregation and aberrant mitosis.
- MCM7 co-localizes with tubulin, suggesting a role in spindle dynamics.
Conclusions:
- MCM7 plays a novel role in regulating mitotic progression and exit.
- MCM7 influences CDK1 activity, cohesin cleavage, and potentially spindle formation.
- These findings suggest MCM7 is involved in ensuring proper cell division by preventing premature cytokinesis.
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