The eukaryotic nucleotide excision repair pathway (original) (raw)
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Sub-cellular biochemistry, 2010
Nucleotide excision repair (NER) is one of the major DNA repair pathways in eukaryotic cells that counteract the formation of genetic damage. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation, and bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to severe diseases, including some forms of cancer. In view of the broad substrate specificity of NER, it is of interest to understand how a certain set of proteins recognizes various DNA lesions in the contest of a large excess of intact DNA. This review focuses on DNA damage recognition, the key and, as yet, most questionable step of NER. Understanding of mechanism of this step of NER may give a key contribution to study of similar processes of DNA damage recognition (base excision repair, mismatch repair) and regulation of assembly of various DNA repair machines. The major models of primary damage recognition and pre-incision comple...
Genetics and Molecular Biology, 2020
Base and nucleotide excision repair (BER and NER) pathways are normally associated with removal of specific types of DNA damage: small base modifications (such as those induced by DNA oxidation) and bulky DNA lesions (such as those induced by ultraviolet or chemical carcinogens), respectively. However, growing evidence indicates that this scenario is much more complex and these pathways exchange proteins and cooperate with each other in the repair of specific lesions. In this review, we highlight studies discussing the involvement of NER in the repair of DNA damage induced by oxidative stress, and BER participating in the removal of bulky adducts on DNA. Adding to this complexity, UVA light experiments revealed that oxidative stress also causes protein oxidation, directly affecting proteins involved in both NER and BER. This reduces the cell's ability to repair DNA damage with deleterious implications to the cells, such as mutagenesis and cell death, and to the organisms, such as cancer and aging. Finally, an interactome of NER and BER proteins is presented, showing the strong connection between these pathways, indicating that further investigation may reveal new functions shared by them, and their cooperation in maintaining genome stability.
Annals of the New York Academy of Sciences, 1994
Recent years have witnessed remarkable progress in the investigative field that embraces how living cells respond to genomic injury. This progress is evidenced by insights about the detailed mechanisms of various DNA repair and damage tolerance mechanisms, the structure of several components of DNA repair "machines," the extent of the evolutionary conservation of DNA repair in eukaryotes, and the emerging relationship between DNA repair and other cellular events that impact on genomic fidelity and integrity.'-' These proceedings contain numerous contributions that address several of these advances in considerable detail. My own comments will focus on recent new insights that derive from the study of nucleotide excision repair (NER) in the yeast Saccharomyces cerevisiae, with a particular emphasis on selected mechanistic considerations and the relationship between DNA repair and other cellular processes.
Oxidative Medicine and Cellular Longevity
The continuous exposure of the human body’s cells to radiation and genotoxic stresses leads to the accumulation of DNA lesions. Fortunately, our body has several effective repair mechanisms, among which is nucleotide excision repair (NER), to counteract these lesions. NER includes both global genome repair (GG-NER) and transcription-coupled repair (TC-NER). Deficiencies in the NER pathway underlie the development of several DNA repair diseases, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Deficiencies in GG-NER and TC-NER render individuals to become prone to cancer and neurological disorders, respectively. Therefore, NER regulation is of interest in fine-tuning these risks. Distinct signaling cascades including the NFE2L2 (NRF2), AHR, PI3K/AKT1, MAPK, and CSNK2A1 pathways can modulate NER function. In addition, several chemical and biological compounds have proven success in regulating NER’s activity. These modulators, particularly the ...
The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage
Nucleic Acids Research, 2020
The six major mammalian DNA repair pathways were discovered as independent processes, each dedicated to remove specific types of lesions, but the past two decades have brought into focus the significant interplay between these pathways. In particular, several studies have demonstrated that certain proteins of the nucleotide excision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the removal of oxidative lesions. This review focuses on recent data showing how the NER proteins, XPA, XPC, XPG, CSA, CSB and UV-DDB, work to stimulate known glycosylases involved in the removal of certain forms of base damage resulting from oxidative processes, and also discusses how some oxidative lesions are probably directly repaired through NER. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we detail how we believe UV-DDB may be the first responder in altering the structure of damage containing-nucleosomes, allow...
Photoreactive DNA as a tool for studying topography of nucleotide excision repair complex
Biopolymers & Cell, 2012
Nucleotide excision repair (NER) is one of the major DNA repair pathways in eukaryotic cells preventing genetic abnormalities caused by DNA damage. NER removes a wide set of structurally diverse lesions such as pyrimidine dimers arising upon UV irradiation and bulky chemical adducts arising upon exposure to environmental carcinogens or chemotherapeutic drugs. In view of the extraordinarily broad substrate specificity of NER, it is of interest to understand how a certain set of proteins recognizes various DNA lesions in the context of a large excess of intact DNA. This review focuses on contribution of photoaffinity labeling technique in the study of DNA damage recognition and following stages resulting in preincision complex assembly, the key and still most unclear steps of NER.