Effects of ethylene oxide and ethylene inhalation on DNA adducts, apurinic/apyrimidinic sites and expression of base excision DNA repair genes in rat brain, spleen, and liver

Recently, a novel gene-deletion method was developed for the crenarchaeal model Sulfolobus islandicus, which is a suitable tool for addressing gene essentiality in depth. Using this technique, we have investigated functions of putative DNA repair genes by constructing deletion mutants and studying their phenotype. We found that this archaeon may not encode a eukarya-type of NER (nucleotide excision repair) pathway because depleting each of the eukaryal NER homologues XPD, XPB and XPF did not impair the DNA repair capacity in their mutants. However, among seven homologous recombination proteins, including RadA, Hel308/Hjm, Rad50, Mre11, HerA, NurA and Hjc, only the Hjc nuclease is dispensable for cell viability. Sulfolobus encodes redundant BER (base excision repair) enzymes such as two uracil DNA glycosylases and two putative apurinic/apyrimidinic lyases, but inactivation of one of the redundant enzymes already impaired cell growth, highlighting their important roles in archaeal DNA repair. Systematically characterizing these mutants and generating mutants lacking two or more DNA repair genes will yield further insights into the genetic mechanisms of DNA repair in this model organism.

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PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes

Biomarkers ◽

10.1080/13547500701671895 ◽

2008 ◽

Vol 13 (1) ◽

pp. 27-40 ◽

Cited By ~ 7

Author(s):

Yu Hu ◽

Gang Li ◽

Xiaonan Xue ◽

Zongcan Zhou ◽

Xiaomei Li ◽

...

Keyword(s):

Dna Repair ◽

Dna Adducts ◽

Chinese Population ◽

Dna Repair Genes ◽

Pah Exposure ◽

Repair Genes

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Modulation of Colorectal Cancer Risk by Polymorphisms in 51Gln/His, 64Ile/Val, and 148Asp/Glu of APEX Gene; 23Gly/Ala of XPA Gene; and 689Ser/Arg of ERCC4 Gene

Gastroenterology Research and Practice ◽

10.1155/2017/3840243 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

L. Dziki ◽

A. Dziki ◽

M. Mik ◽

I. Majsterek ◽

J. Kabzinski

Keyword(s):

Colorectal Cancer ◽

Dna Repair ◽

Malignant Transformation ◽

Excision Repair ◽

Control Group ◽

Dna Repair Genes ◽

Nucleotide Excision ◽

Base Excision ◽

The Impact ◽

Repair Genes

Polymorphisms in DNA repair genes may affect the activity of the BER (base excision repair) and NER (nucleotide excision repair) systems. Using DNA isolated from blood taken from patients (n=312) and a control group (n=320) with CRC, we have analyzed the polymorphisms of selected DNA repair genes and we have demonstrated that genotypes 51Gln/His and 148Asp/Glu of APEX gene and 23Gly/Ala of XPA gene may increase the risk of colorectal cancer. At the same time analyzing the gene-gene interactions, we suggest the thesis that the main factor to be considered when analyzing the impact of polymorphisms on the risk of malignant transformation should be intergenic interactions. Moreover, we are suggesting that some polymorphisms may have impact not only on the malignant transformation but also on the stage of the tumor.

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XRCC1 Arg399Gln Genetic Polymorphism in a Turkish Population

International Journal of Toxicology ◽

10.1080/10915810600870567 ◽

2006 ◽

Vol 25 (5) ◽

pp. 419-422 ◽

Cited By ~ 11

Author(s):

Neslihan Aygün Kocabaş ◽

Bensu Karahalil

Keyword(s):

Dna Repair ◽

Dna Adducts ◽

Excision Repair ◽

Rflp Analysis ◽

Turkish Population ◽

Dna Repair Genes ◽

Xrcc1 Gene ◽

Repair Capacity ◽

Repair Genes

Humans are routinely exposed to mutagenic and carcinogenic chemicals. These chemicals can form DNA adducts in vivo and thus lead to DNA damage. The integrity of most of the so-damaged DNAs is typically restored as a consequence of the action of certain DNA-repairing enzymes. In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. XRCC1 is a base-excision repair protein that plays a central role in the repair of DNA base damage and strand breaks. Amongst the known genetic polymorphisms of the DNA-repair genes, X-ray repair cross-complementing groups 1 and 3 ( XRCC1 and XRCC3) have been studied most commonly. Inconsistent results have been reported regarding the associations between the Arg399Gln (exon 10) polymorphism of XRCC1 and either functional significance or the risk of tobacco-associated cancers. The Gln allele of this polymorphism was associated with higher levels of DNA adducts. Therefore we genotyped one of the polymorphism of XRCC1, Gln allele. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. There has been no information on interindividual variability of Arg399Gln genotype in the Turkish population. Due to the association between the Arg399Gln polymorphism of XRCC1 and the risk of tobacco-associated cancers, we preferred to evaluate the allelic frequencies of Arg399Gln genotype than the other polymorphisms in XRCC1 gene in healthy Turkish population by polymerase chain reaction–restriction fragment polymorphism (PCR-RFLP) analysis to enable to show interindividual differences and compare to other populations.

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