The Multiple Facets of ATRX Protein

SIMPLE SUMMARY: The gene encoding for the epigenetic regulator ATRX is gaining a prominent position among the most important oncosuppressive genes of the human genome. ATRX gene somatic mutations are found across a number of diverse cancer types, suggesting its relevance in tumor induction and progression. In the present review, the multiple activities of ATRX protein are described in the light of the most recent literature available highlighting its multifaceted role in the caretaking of the human genome. ABSTRACT: ATRX gene codifies for a protein member of the SWI-SNF family and was cloned for the first time over 25 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability called Alpha Thalassemia/mental Retardation syndrome X-linked (ATRX) syndrome. Since its discovery as a helicase involved in alpha-globin gene transcriptional regulation, our understanding of the multiple roles played by the ATRX protein increased continuously, leading to the recognition of this multifaceted protein as a central “caretaker” of the human genome involved in cancer suppression. In this review, we report recent advances in the comprehension of the ATRX manifold functions that encompass heterochromatin epigenetic regulation and maintenance, telomere function, replicative stress response, genome stability, and the suppression of endogenous transposable elements and exogenous viral genomes.