Mechanotransduction tuned by intermediate filaments promotes DNA repair in stiff environments

Cells on rigid substrates recruit DNA repair factors more efficiently and repair DNA breaks faster, with hemidesmosomal integrins, intermediate filaments, the LINC complex, and YAP mediating the mechanogenomic response.

• Why it matters: Tissue stiffness in dense, collagen-rich breast environments is linked to cancer risk, but how rigidity affects genome maintenance and DNA damage response remains unclear.
• What they did: The study tested cells in stiff versus rigid substrate contexts and used mechanistic perturbations implicating hemidesmosomal integrins, intermediate filaments, the LINC complex, and YAP in DNA repair factor recruitment and break repair kinetics.
• The result: Rigid contexts favor survival of cells with DNA damage, which may contribute to somatic mutation accumulation, supported by RNAseq analyses of normal breast tissue.

AI summary of the abstract · may contain errors · not medical advice · read the paper.