Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

Abstract

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

“…This property is important in the context of telomerase action, as four-stranded DNA is not a substrate for that enzyme. The second consequence follows from the fact that guanine has the highest number of oxidationsensitive sites among all DNA bases [48]. Therefore, telomeres may be remarkably prone to oxidative stress, a common factor of AMD pathogenesis.…”

Impact of Oxidative DNA Damage and the Role of DNA Glycosylases in Neurological Dysfunction

“…Base excision repair (BER) is the major pathway for repair of non-bulky oxidative DNA damage such as SSBs and base lesions, while cyPU lesions are exclusively repaired via nucleotide excision repair (NER) [ 21 , 22 ]. Nucleotide excision repair (NER) competes with BER in the repair of certain oxidatively generated guanine lesions (reviewed in [ 23 ]). The efficiency of NER and BER is determined by the type of lesion, type of DNA, and nuclear concentrations of lesion-recognizing enzymes within the two pathways.…”

The Physical Chemistry and Chemical Physics (PCCP) Section of the International Journal of Molecular Sciences in Its Publications: The First 300 Thematic Articles in the First 3 Years

“…In this Thematic Area, 56 articles have been published [ 48 , 64 , 104 , 108 , 110 , 124 , 195 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 , 299 , 300 ], an...…”

“…A more detailed examination shows that, in this direction, as well as in the previous ones, articles in which the objects of research are organic materials clearly prevail over articles in which the objects of research are inorganic materials (36 and 20, respectively). Wherein, the overwhelming majority of articles of the “organic” profile are, in one way or another, connected with the participation of the objects with a biological origin; these include [ 64 , 124 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 274 , 277 , 278 , 282 , 284 , 289 , 291 , 292 , 293 , 294 , 295 , 296 , 298 , 299 , 300 ] and the processes in abiogenic organic materials were considered only in [ 48 , 195 , 266 , 271 , 272 , 273 , 283 , 288 , 290 ]. The thematic focus of these works, as well as the chemical compounds studied in them, is also very diverse, and even a simple listing of them here is clearly beyond the scope of this article, too.…”

“…In [ 271 ], a three-symmetric trioxotriangulene derivative with three pyridyl groups as coordination centers was synthesized, which, according to the cyclic voltammetry data, showed a multistep redox ability from neutral radical to radical tetraanionic forms. The physical and physicochemical processes in organic materials are also devoted to 9 out of 11 review articles belonging to Thematic Area 9, namely [ 254 , 261 , 274 , 289 , 291 , 293 , 298 ]; all of these reviews are, in one way or another, related to biological systems. It is worth noting, however, a review article [ 274 ] that is devoted to such an extremely urgent problem today, the fight against the “plague of the XXI century”, the coronavirus infection (COVID-19), in particular the timely detection of this disease and the development of methods for its treatment using nanomaterials and/or nanotechnology.…”