2.2.7. DNA Damage and Repair

Insufficient response to DNA damage leads to various insults that enhance apoptosis or result in a dysfunctional phenotype [59]. Several studies have shown a maladaptive response of renal tubular cells during AKI and suggest that an insufficient response to DNA damage could accelerate CKD [10,59,60]. Many studies have described DNA damage as a hallmark of various forms of renal damage characterized by dysfunctional cell cycle proteins of G1/S and G2/M checkpoints and subsequent cell cycle arrest through the activation of p53 or p21 signaling cascades [61,62]. These mutated cells become senescent and have a specific secretome-defined phenotype (senescence-associated secretory phenotype; SASP), which is accompanied by genomic damage and epigenetic abnormalities [63]. The synthesis and release of SASP factors is associated with the activation of the transcription factors, nuclear factor kappa B (NF-κB), and CCAAT enhancer binding protein β (C/EBPβ) [64]. Thus, both altered DNA damage response and NF-κB activation significantly contribute to establishing and maintaining SASP, which produces and releases more senescent secretomes, contributing to functional deterioration of neighboring cells and accelerating the process of cellular death.
