GENOME STABILITY REGULATION DURING MITOTIC CHECKPOINT FAILURE IN CANCER CELL PROGRESSION

Abstract

Background: Genome stability is essential for accurate chromosomal segregation and prevention of malignant transformation during cell division. Mechanisms of the mitotic checkpoint, including the spindle assembly checkpoint (SAC), are essential for the regulation of chromosome alignment and genomic integrity. These checkpoints, when failed, contribute to chromosomal instability, aneuploidy and progression of cancer.
Objective: The aim of this study was to investigate the regulation of genome stability upon mitotic checkpoint failure and to evaluate its effect on chromosomal instability and cancer cell progression.
Methods: Comparative analyses were performed using normal epithelial cells and cancer cell lines treated with CRISPR-Cas9 mediated checkpoint disruption, RNA interference and kinase inhibitors. The functional assays included live-cell imaging, RNA sequencing, immunofluorescence microscopy and DNA damage analysis in order to assess mitotic defects, aneuploidy and cellular responses.

Findings: Experimental results demonstrated a 40–60% increase in chromosomal instability and elevated γ-H2AX DNA damage levels following BUB1 and MAD2 checkpoint disruption. Transcriptomic profiling revealed dysregulation of Aurora kinase and PLK1 signaling pathways associated with increased tumor cell proliferation and mitotic abnormalities.

Conclusion: The findings indicate that mitotic checkpoint failure significantly compromises genome stability and promotes cancer progression. Understanding checkpoint-associated genomic instability may support development of targeted therapeutic strategies and precision oncology approaches.