UBA52 Mediates ribosomal DNA stability under hexavalent chromium exposure in occupational workers and cellular models

Abstract

Hexavalent chromium [Cr(VI)] exposure poses substantial environmental and health risks, especially in occupational settings, where it has been linked to genomic instability. Our previous research demonstrated that Cr(VI) exposure could induce DNA copy number (CN) variation. Here, we examined the role of Ubiquitin A-52 ribosomal protein fusion product 1 (UBA52) in stabilizing rDNA CN under Cr(VI) exposure by analyzing data from Cr(VI)-exposed workers and matched controls. Results showed significantly elevated blood Cr levels, increased γH2AX expression, and higher rDNA CN in exposed individuals, alongside upregulated UBA52 mRNA and protein levels. Spearman and regression analyses identified positive correlations between Cr levels and UBA52 expression, and between UBA52 expression and rDNA CN. In vitro studies in BEAS-2BR and HeLa cells confirmed Cr(VI)-induced upregulation of UBA52, and UBA52 knockdown led to rDNA CN instability in cells. These findings highlight that UBA52 contributes to preserving rDNA stability in the face of Cr(VI)-induced genomic stress, providing valuable insights into molecular responses to environmental Cr(VI) exposure.