Figure 2.

Cr(VI) disrupts transcriptional regulatory mechanisms. The reduction of intracellular Cr(VI) yields reactive intermediates that damage several key macromolecules and form bulky DNA lesions, such as Cr–DNA adducts and protein–Cr–DNA crosslinks, resulting in widespread DNA double-strand breaks, arrest of RNA polymerase-II (RNAPII) transcription elongation and global chromatin disruption. Direct effects of Cr(VI) on proteins such as transcription factors lead to transcriptional disruption in pathways regulated by these proteins. The altered chromatin configuration arising from Cr(IV) bulky lesions gives way to conflicting epigenetic marks (altered DNA methylation, histone modifications, and non-coding RNA profiles) that not only inhibit transcription of inducible genes but also destabilize the global transcription machinery.