A Systems-Level Structural Dependency Model of DNA Integrity: Operational Collapse as the Precursor to Oncogenesis

Biological systems maintain genomic integrity through three upstream structural environments: bioenergetic equilibrium, proteostasis capacity, and chromatin-based structural protection. These domains form a universal architecture required for accurate replication, repair, and long-term DNA stability. Within this framework, genetic mutations arise not as primary drivers of disease but as downstream residues of structural collapse in these environments. This structural interpretation unifies genetic inheritance, environmental influence, and cellular maintenance into a single causal model: inherited variants represent structural capacity, environmental pressures impose structural load, and disease emerges when load exceeds capacity. This model accounts for divergent disease trajectories among individuals with similar genetic variants, the acceleration of genomic instability under environmental stress, and the partial correction of inherited structural weaknesses during embryonic reconstruction of energetic, proteostatic, and chromatin systems. The framework is novel because molecular biology lacks a unified architecture linking genetics, environment, and cellular function. If validated, this structure has the potential to provide a predictive, cross-domain causal model that may exceed the explanatory scope of mutation-centric and pathway-centric approaches. By establishing DNA integrity as an emergent property of upstream structural environments, this work offers a conceptual foundation for future physics-informed measurement strategies that complement existing molecular modeling methods.