Molecular Mechanism of Global Genome Nucleotide Excision Repair

Abstract

Nucleotide excision repair (NER) is a multistep process that recognizes and eliminates a wide spectrum of damage causing significant distortions in the DNA structure, such as UV-induced damage and bulky chemical adducts. The consequences of defective NER are apparent in the clinical symptoms of individuals affected by three disorders associated with reduced NER capacities: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). These disorders have in common increased sensitivity to UV irradiation, greatly elevated cancer incidence (XP), and multi-system immunological and neurological disorders. The eucaryotic NER system eliminates DNA damage by the excision of 24–32 nt single-strand oligonucleotides from a damaged strand, followed by restoration of an intact double helix by DNA repair synthesis and DNA ligation. About 30 core polypeptides are involved in the entire repair process. NER consists of two pathways distinct in initial damage sensor proteins: transcription-coupled repair (TC-NER) and global genome repair (GG-NER). The article reviews current knowledge on the molecular mechanisms underlying damage recognition and its elimination from mammalian DNA.

Association between the ERCC1 rs11615 polymorphism and clinical outcomes of oxaliplatin-based chemotherapies in gastrointestinal cancer: a meta-analysis

“…The mechanism of action of platinum agents is based on the formation of DNA adducts that result in the alteration of the DNA structure and, eventually, the inhibition of DNA replication and transcription. 32 Hence, the expression of genes involved in the mechanisms of DNA repair has been studied as a possible predictive factor in patients treated with platinum-based chemotherapy. 33 ERCC1, which has a variety of gene forms, is the lead enzyme in the NER DNA repair pathway.…”

DNA Damage/Repair Management in Cancers

“…Nucleotide excision repair (NER) is one of the major DNA repair pathways to protect the cells against DNA lesions that vary structurally and chemically. The most prevalent lesions are produced from additions of bulky covalent adducts initiated by nitrogenous bases and are affected by UV light, ionizing irradiation, electrophilic chemical mutagens, drugs and chemically active endogenous metabolites [93].…”

Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria‐related disorders

“…Other diseases featuring premature ageing traits are associated with defects in the DNA repair machinery caused by mutations in genes encoding NER proteins. NER is a multistep mechanism able to identify and restore nucleotidic changes due to ultraviolet (UV) rays or chemical compounds, modifying DNA structure . Mutations occurring to the proteins involved in this machinery are responsible for the onset of genetic disorders, and all feature in the development of cancers and increased sensitivity to light.…”