Cdk1-dependent lamin aggregation underlies oxidative stress-induced nuclear shape abnormalities.

Area of Science:

• Cell Biology
• Cancer Research
• Molecular Biology

Background:

• Altered nuclear morphology is a hallmark of cancer and impacts tumor prognosis.
• Reactive oxygen species (ROS) are known to induce nuclear changes, but the mechanisms are unclear, especially during nuclear assembly.
• Mitotic cells, with their dynamic nuclear envelope, may be particularly vulnerable to ROS-induced nuclear deformation.

Purpose of the Study:

• To investigate the mechanism by which ROS affect nuclear morphology during mitosis.
• To explore the role of hydrogen peroxide (H2O2) in mitotic nuclear assembly and deformation.
• To elucidate the relationship between ROS, Cdk1 activity, and lamin dynamics.

Main Methods:

• Exposure of mitotic cells to hydrogen peroxide (H2O2).
• Analysis of lamin aggregation and nuclear morphology.
• In vitro kinase assays to assess Cdk1 activity and lamin phosphorylation.
• Investigating the effect of Cdk1 activity restoration on lamin aggregation.

Main Results:

• H2O2 exposure in mitotic cells led to persistent lamin aggregates and aberrant nuclear morphology.
• H2O2 dampened Cdk1 activity, reducing lamin phosphorylation and causing aggregation.
• Restoring Cdk1 activity rescued lamin phosphorylation and mitigated aggregation.
• Lamin aggregation during mitotic entry correlated with premature reassembly, disrupting nuclear envelope formation.

Conclusions:

• ROS-mediated perturbation of Cdk1 activity during early mitosis triggers lamin aggregation.
• This aggregation disrupts lamin reassembly and nuclear envelope formation, leading to altered nuclear morphology.
• The study reveals a novel mechanism of ROS-induced nuclear architecture disruption via Cdk1 modulation during mitosis.