Participation of heat shock proteins in DNA repair mechanisms in cancer

Abstract

Heat shock proteins (HSPs) are well known as molecular chaperones, playing important roles in cellular metabolism, escorting other proteins during aggregation, disaggregation, folding, and unfolding. They have been classified in families according to their molecular weight, i.e. HSPA (HSP70) and HSPH (HSP110), HSP90/HSPC, HSPD1 (HSP60), DNAJ (HSP40), and HSPB (small heat shock proteins including HSP27). HSPs are produced under normal conditions (constitutive) and in response to various stressful conditions/agents such as heat (inducible form). Several HSPs have been involved in cytoprotection, having antiapoptotic roles, and in addition some have been involved in drug resistance to antineoplastic drugs. More recently, it has been also studied the relationship of the HSPs with DNA repair proteins. DNA is constantly subject to numerous insults from endogenous sources (cellular metabolism) and exogenous sources (environmental agents), if this damage is not corrected can lead to genome instability and cancer. Fortunately, our cells count with several DNA-repair pathways to correct the DNA damage and to prevent its consequences. Although the participation of HSPs in DNA repair has received little attention, they are now receiving more interest as possible targets for cancer therapy. Here, we review the participation of HSPs in DNA repair pathways and their implications in cancer therapy and drug sensitivity. Some of the HSPs can travel to the nucleus and it is clear that although the HSPs are not capable of repairing the DNA damages by themselves, they efficiently contribute to the different mechanisms of DNA repair as part of their molecular chaperone capabilities, interacting with DNA repair proteins producing their stimulation and reactivation.