Mayra L. Sottile & Silvina B. Nadin
Received: 14 July 2017 /Accepted: 13 September 2017 /Published online: 26 September 2017 Cell Stress Society International 2017
Heat shock proteins (HSPs), also known as molecular chaperones, participate in important cellular processes, such as protein aggregation, disaggregation, folding, and unfolding. HSPs have cytoprotective functions that are commonly explained by their antiapoptotic role. Their involvement in anticancer drug resistance has been the focus of intense research efforts, and the relationship between HSP induction and DNA repair mechanisms has been in the spotlight during the past decades. Because DNA is permanently subject to damage, many DNA repair pathways are involved in the recognition and removal of a diverse array of DNA lesions. Hence, DNA repair mechanisms are key to maintain genome stability. In addition, the interactome network of HSPs with DNA repair proteins has become an exciting research field and so their use as emerging targets for cancer therapy. This article provides a historical overview of the participation of HSPs in DNA repair mechanisms as part of their molecular chaperone capabilities.
Heat shock proteins (HSPs) have been extensively studied since their discovery in the early 1960s by Ferruccio Ritossa (Ritossa and Vonborstel 1964). These highly conserved molecular chaperones are present in all living cells and have been implicated in multiple physiological processes. They are known as key players in processes associated with development, differentiation, survival, aging, and death. At the cellular level, they participate in protein homeostasis, preventing protein denaturation and unfolding under normal and stressful conditions (e.g., high temperature, hypoxia, heavy metals, chemical agents, and antineoplastic drugs) (Macario and Conway de Macario 2007). On the other hand, HSPs are commonly overexpressed in tumor cells, and they are known as Bchaperones of tumorigenesis^ because of their functions in promoting cancer cell proliferation and apoptosis inhibition (Calderwood et al. 2006). HSPs have also been involved in resistance to chemotherapy and radiotherapy (Wu et al. 2017). HSPs were traditionally classified according to their molecular weight, but to avoid confusions because of the expanding number of members in the families, the nomenclature system recommended by the Human Genome Organization (HUGO) Gene Nomenclature Committee was adopted for all HSPs. It includes HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), and HSPB (small HSP) as well as HSPD/E (HSP60/HSP10) and CCT (TRiC) for the human chaperonin families (Kampinga et al. 2009). The expression of HSPs is transcriptionally regulated by heat shock factors (HSFs), which can bind to sequences located upstream of HSP genes called heat shock elements (HSEs) to induce gene expression (Akerfelt et al. 2010).