Molecular chaperones in DNA repair mechanisms: Role in genomic instability and proteostasis in cancer

Cells are exposed to several environmental or chemical stressors that may cause DNA damage. DNA damage alters the normal functioning of the cell and contributes to several diseases, including cancer. Cells either induce DNA damage repair pathways or programmed cell death pathways to prevent disease formation depending on the severity of the stress and the damage caused. The DNA repair mechanisms are crucial to maintaining genome stability. During this adaptive response, the heat shock proteins (HSPs) are the key players. HSPs are overexpressed during genotoxic stress, but the role of different molecular players in the interaction between HSPs and DNA repair proteins is still poorly understood. As DNA damage promotes genomic instability and proteotoxic stress, modulating the protein quality control systems like the HSPs network could be a promising strategy for targeting disease pathologies associated with genomic instability, such as cancer. Hence, this review highlights the role of HSPs in DNA repair pathways. Further, the review also provides an outlook on the role of genomic instability and protein homeostasis in cancer, which is crucial to understanding the mechanisms behind its survival and developing novel targeted therapies.