Nucleotide excision repair II: from yeast to mammals

doi:10.1016/0168-9525(93)90121-W

Trends in Genetics

Volume 9, Issue 6, June 1993, Pages 211-217

https://doi.org/10.1016/0168-9525(93)90121-W Get rights and content

Abstract

An intricate network of repair systems safeguards the integrity of genetic material, by eliminating DNA lesions induced by numerous environmental and endogenous genotoxic agents. Nucleotide excision repair (NER) is one of the most versatile DNA repair systems. Deficiencies in this process give rise to the classical human DNA repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome (CS), and to a recently recognized disease called PIBIDS, a photosensitive form of the brittle hair disorder trichothiodystrophy. This is the second of a two-part review on NER. Part I (in the previous issue of TIG) concentrated on the main characteristics of the NER pathway of E. coli and yeast. Part II compares the mammalian and yeast systems, and attempts to integrate current knowledge on the eukaryotic pathway to suggest an outline for the reaction mechanism.

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Cited by (284)

Helicases required for nucleotide excision repair: structure, function and mechanism
2023, Enzymes
Nucleotide excision repair (NER) is a major DNA repair pathway conserved from bacteria to humans. Various DNA helicases, a group of enzymes capable of separating DNA duplex into two strands through ATP binding and hydrolysis, are required by NER to unwind the DNA duplex around the lesion to create a repair bubble and for damage verification and removal. In prokaryotes, UvrB helicase is required for repair bubble formation and damage verification, while UvrD helicase is responsible for the removal of the excised damage containing single-strand (ss) DNA fragment. In addition, UvrD facilitates transcription-coupled repair (TCR) by backtracking RNA polymerase stalled at the lesion. In eukaryotes, two helicases XPB and XPD from the transcription factor TFIIH complex fulfill the helicase requirements of NER. Interestingly, homologs of all these four helicases UvrB, UvrD, XPB, and XPD have been identified in archaea. This review summarizes our current understanding about the structure, function, and mechanism of these four helicases.
Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: A case-control study
2021, Environmental Pollution
Humans are extensively exposed to polycyclic aromatic hydrocarbons (PAHs) daily via multiple pathways. Epidemiological studies have demonstrated that occupational exposure to PAHs increases the risk of lung cancer, but related studies in the general population are limited. Hence, we conducted a case-control study among the Chinese general population to investigate the associations between PAHs exposure and lung cancer risk and analyze the modifications of genetic polymorphisms in DNA repair genes. In this study, we enrolled 122 lung cancer cases and 244 healthy controls in Wuhan, China. Urinary PAHs metabolites were determined by gas chromatography-mass spectrometry, and rs25487 in X-ray repair cross-complementation 1 (XRCC1) gene was genotyped by the Agena Bioscience MassARRAY System. Then, multivariable logistic regression models were performed to estimate the potential associations. We found that urinary hydroxynaphthalene (OH-Nap), hydroxyphenanthrene (OH-Phe) and the sum of hydroxy PAHs (∑OH-PAHs) levels were significantly higher in lung cancer cases than those in controls. After adjusting for gender, age, BMI, smoking status, smoking pack-years, drinking status and family history, urinary ∑OH-Nap and ∑OH-Phe levels were positively associated with lung cancer risk, with dose-response relationships. Compared with those in the lowest tertiles, individuals in the highest tertiles of ∑OH-Nap and ∑OH-Phe had a 2.13-fold (95% CI: 1.10, 4.09) and 2.45-fold (95% CI: 1.23, 4.87) increased risk of lung cancer, respectively. Effects of gender, age, smoking status and smoking pack-years on the associations of PAHs exposure with lung cancer risk were shown in the subgroup analysis. Furthermore, associations of urinary ∑OH-Nap and ∑OH-PAHs levels with lung cancer risk were modified by XRCC1 rs25487 (P_interaction ≤ 0.025), and were more pronounced in wild-types of rs25487. These findings suggest that environmental exposure to naphthalene and phenanthrene is associated with increased lung cancer risk, and polymorphism of XRCC1 rs25487 might modify the naphthalene exposure-related lung cancer effect.
Influence of chromatin remodeling in the removal of UVC-induced damage in TCR proficient and deficient Chinese hamster cells
2018, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Citation Excerpt :
Both lesions are exclusively removed by nucleotide excision repair (NER) system in mammalian cells [1,2]. Two sub-pathways have been recognized in the nucleotide excision repair system, named global genomic repair or GGR and transcription coupled repair or TCR [3–5]. The consequences of a defect in any of the NER proteins are implicated in three rare recessive syndromes: Xeroderma Pigmentosum, Cockayne’s Syndrome (CS) and the photosensitive form of the brittle hair disorder Trichothiodystrophy [6].
In mammalian cells, nucleotide excision repair system is constituted of two sub-pathways, global genomic repair (GGR) and transcription coupled repair (TCR). Deficiency of TCR pathway leads to Cockyane syndrome (CS) which is a rare human autosomal recessive disorder. Owing to the pivotal role of CSB gene in TCR, it’s mutation causes severe repair and transcriptional defects in CSB patients. CSB protein belongs to the ATP chromatin remodeling complex, hence presumably an improper chromatin remodeling in CSB cells could be at the source of inefficient removal of pyrimidine dimers (CPDs) after UVC exposure in these patients. In this study, we evaluated the role of chromatin remodeling process on UVC induced CPDs and the ensuing effect on chromosomal aberrations in UV61 cells (TCR deficient) and its parental cell line, AA8 (TCR proficient). We observed that post 2 h UVC irradiation, both cell lines underwent pronounced chromatin relaxation but was lower in CSB deficient UV61 cells. Since the deficiency in chromatin remodeling in CSB-mutated cells was accompanied by a decrease in the histone acetylation level, the histone deacetylase inhibitor trichostatin A (TSA) was employed to improve the removal of UVC-induced lesions by increasing the histone acetylation level. Contrary to expectations, TSA increased the induction of chromosomal aberrations and apoptotic cells along with amounts of CPDs after UVC-irradiation, indicating that changes in histone acetylation levels might contribute to the failure in the removal of UVC-induced lesions. Also, it has been shown earlier that the expression of genes regulated by CSB is affected by the increase in the acetylation level produced by TSA. Taken all together, we hypothesize that failure in the removal of UVC induced lesions in CSB-deficient cells can be caused by an imbalance in histone acetylation levels leading to chromatin conformation changes and hence interaction defects among repair proteins and DNA lesions.
Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk
2018, Clinical Colorectal Cancer
Citation Excerpt :
Besides the various targets, both subpathways require a different set of proteins to recognize a lesion site and initiate repair. Details has been reviewed in many articles.11-13 Xeroderma pigmentosum (XP) disease which causes UV-sensitivity in patients, is an excellent example of genetic impairment that shows an inability to perform ggNER, had a great impact on the discovery and study of NER.
Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk.
The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts.
We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene.
Taken together, our findings suggest a potential role for NER in CRC.
BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management
2017, DNA Repair
Citation Excerpt :
DNA contained in both the nuclear and mitochondrial cellular compartments is subject to damage from multiple sources [1–3]. Diverse classes of DNA damage are caused by exogenous sources such as UV, ionizing radiation, alkylating agents, and heavy metals [4–8]. Endogenous sources of damage such as reactive oxygen species (ROS), are generated during normal metabolic functions as well as various cellular transactions [2,9].
DNA base damage and non-coding apurinic/apyrimidinic (AP) sites are ubiquitous types of damage that must be efficiently repaired to prevent mutations. These damages can occur in both the nuclear and mitochondrial genomes. Base excision repair (BER) is the frontline pathway for identifying and excising damaged DNA bases in both of these cellular compartments. Recent advances demonstrate that BER does not operate as an isolated pathway but rather dynamically interacts with components of other DNA repair pathways to modulate and coordinate BER functions. We define the coordination and interaction between DNA repair pathways as pathway crosstalk. Numerous BER proteins are modified and regulated by post-translational modifications (PTMs), and PTMs could influence pathway crosstalk. Here, we present recent advances on BER/DNA repair pathway crosstalk describing specific examples and also highlight regulation of BER components through PTMs. We have organized and reported functional interactions and documented PTMs for BER proteins into a consolidated summary table. We further propose the concept of DNA repair hubs that coordinate DNA repair pathway crosstalk to identify central protein targets that could play a role in designing future drug targets.
OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility
2013, Toxicology Letters
Citation Excerpt :
The most common form of oxidative DNA damage induced by ROS is the 8-hydroxydeoxyguanine (8-OHdG) which is highly mutagenic due to yielding G:C to T:A transversion by errors during DNA replication, and increased 8-OHdG levels have been observed in semen of infertile men (Dantzer et al., 2003; Meseguer et al., 2008). Therefore, the maintaining genome integrity seems essential, and DNA repair systems play a critical role in protecting the genome from insults caused by carcinogenic agents, such as those found in tobacco smoke (Hoeijmakers, 1993). In mammal cells, the 8-OHdG lesions are subject to the base excision repair (BER) pathway, which is specialized to remove the oxidatively damaged bases and is initiated by OGG1 (Barnes and Lindahl, 2004).
8-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years ≥5 but not among those subjects with pack-years < 5 (pack-years = packs smoked per day × years as a smoker). Further analysis based on the case–control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR = 1.35, 95% CI: 1.01–1.82; trend P < 0.001). Furthermore, we found a significant gene–environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (P_interation = 0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.

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Trends in Genetics

ReviewNucleotide excision repair II: from yeast to mammals

Abstract

Trends Genet.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Exp. Cell Res.

Mutat. Res.

Cell

Cell

Mutat. Res.

Cell

Cell

Mutat. Res.

Mutat. Res.

Cell

Mutat. Res.

Cell

Cell

Carcinogenesis

Am. J. Med. Genet.

Cancer Rev.

Review
Nucleotide excision repair II: from yeast to mammals