Rising from the fragments: a multi-factorial regulatory framework of DNA damage response in Deinococcus radiodurans

Understanding the coordinated regulation of gene expression in response to environmental challenges is critical for unravelling the resistance strategies of the extremophiles that endure extreme habitats. Deinococcus radiodurans is a notable extremophile for rebuilding entire genome from the fragmented DNA, a property that enables it to withstand acute exposure to high levels of DNA-damaging agents, including gamma radiation, ultraviolet (UV) rays, desiccation, and chemical mutagens. In the context of DNA damage, a variety of DNA lesions from base damages to double strand breaks are acted upon by appropriate DNA repair pathways which operate either in tandem or in a sequential manner to efficiently restore the entire genome and restart normal growth. To achieve a high-regulatory specificity, a multi-factorial regulatory mechanism is required to activate or repress target pathway genes in vivo, in a dose and time dependent manner. Several studies have explored a role of cis-acting elements including genomic sequences like promoters, enhancers, or operators, structural elements, or trans-acting factors such as transcriptional regulators or non-coding RNAs (ncRNAs) in the regulation of DNA damage response. This review explores the intricate regulatory networks employed by D. radiodurans, offering a comprehensive overview of its DNA damage response mechanisms. These insights help shed light on the molecular strategies that enable this organism to thrive in extreme environments. The knowledge gaps which need the focus of future research are discussed.