ENGINEERING CHROMOSOMAL STABILITY MECHANISMS TO PREVENT GENOME REARRANGEMENTS IN CANCER CELLS

Abstract

Background:  Chromosomal instability and genome rearrangements are major drivers of cancer progression, tumor heterogeneity and therapeutic resistance. Engineering mechanisms that promote chromosomal stability could be an effective strategy to maintain genomic integrity in cancer cells.

Objective: The aim of the study was to investigate synthetic biology and genome engineering approaches to improve chromosomal stability and prevent genome rearrangements in cancer cells.

Methodology: Human breast and colon cancer cell lines were engineered with CRISPR-Cas9 mediated modulation of DNA repair pathways, telomere maintenance systems and mitotic checkpoint proteins. Experimental analyses included fluorescence microscopy, chromosome instability assays, micronuclei quantification, DNA damage response analysis and telomere integrity assessment. The frequency of genome rearrangement and levels of chromosomal aberrations were compared in engineered vs. untreated control cells.

Findings: Engineered cancer cells showed 185% more DNA repair-associated stability and 162% more telomere integrity. The engineered cells exhibited a significant reduction of the frequency of chromosomal aberration and micronuclei formation compared to controls. Furthermore, enhanced mitotic checkpoint control reduced errors of chromosomal segregation and improved genomic stability.

Conclusion: Effective engineering of chromosomal stability mechanisms suppresses genome rearrangements and enhances genomic integrity in cancer cells, indicating potential therapeutic applications in precision oncology and cancer genome stabilization strategies.