Exploring DNA Damage and Repair Mechanisms: A Review with Computational Insights

The NER (nucleotide excision repair) mechanism is employed to repair the damage by creating large adducts and intra-strand crosslinks when UV light and polycyclic aromatic hydrocarbons damage DNA. The nucleotide excision respirasome, a multi-protein complex, performs the NER process in mammals [25,26,27]. The excision of about twenty-eight nucleotide DNA segments furnishing the damaged site is the primary process in eukaryotic NER [27,28]. The two different sub-pathways of global genome repair (GGR) and transcription-coupled repair (TCR) make up NER in mammalian cells [29,30,31]. The XPC-hHR23 complicated is the primary DNA damage key factor in GGR. Another GGR DNA damage binding factor (DDB) [32,33] is a DNA damage sensor. The TFIIHp62 subunit interacts with the damage recognition complex XPC-HR23B in GGR to transport it to the damaged area [34,35]. In terms of liberating damaged DNA, XPB seems to have less helicase activity than XPD. GGR and TCR need this 36 kDa protein [36,37]. RPA, ERCC1, and TFIIH are all known to interact with damaged DNA. RPA and ERCCC investigations have shown that XPA preferentially binds to damaged DNA. The TFIIH helicase subunits’ generated ssDNA intermediate is stabilized by this protein’s ssDNA binding activity [38]. Following DNA synthesis, a twin insertion occurs on the damaged surface because of the sequential recruitment of the XPG and XPF-ERCC1 nuclear. XPG and XPF-ERCC1 are structurally specific nucleases that prefer to hydrolyze double-stranded substrates near ssDNA and sDNA junctions [39], ensuring the proper localization of these proteins to the site of injury and stimulating their junction-breaking endonuclease activity [40]. The DNA substrate bladder, valves, arms, and stem loops are only a few of the DNA substrates that XPG, a 133 kDa protein, affects [41]. The XPG protein possesses two highly conserved nucleic acid motifs spaced apart by a region that aids protein interactions. A protein of 37 kDa in molecular weight, PCNA belongs to the DNA sliding clamp family. In an ATP-dependent process, RFC assembles PCNA on the DNA template by ideally aligning with the 3′-hydroxyl ends of the DNA primer. Polymerase interactions with PCNA and RFC make it possible to synthesize DNA accurately and effectively [42]. POL η and POL ι, in the polymerase β family, exhibit intrinsic exonuclease activity (3′–5′) to correct for reading. The four subunits of mammals form the POL complex are 50, 12, 68, 125, and 68 kDa [43].