Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes

2013 ◽  
Vol 41 (1) ◽  
pp. 405-410 ◽  
Author(s):  
Changyi Zhang ◽  
Bin Tian ◽  
Suming Li ◽  
Xiang Ao ◽  
Kevin Dalgaard ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genetic Manipulation ◽  
Excision Repair ◽  
Model Organism ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Sulfolobus Islandicus ◽  
Base Excision ◽  
Repair Genes

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.

The genotype distribution of the XRCC1gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3761-3766 ◽  
Author(s):  
Claire Seedhouse ◽  
Rowena Bainton ◽  
Michael Lewis ◽  
Alexander Harding ◽  
Nigel Russell ◽  
...  
Keyword(s):  
Dna Repair ◽  
Protective Effect ◽  
Excision Repair ◽  
Acute Myeloblastic Leukemia ◽  
Polymorphism Analysis ◽  
Genotype Distribution ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Repair Genes

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML). We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD. We also assessed the incidence of a functional polymorphism in theNQO1 gene, which is involved in protection of cells from oxidative damage. We genotyped the polymorphisms by using polymerase chain reaction–restriction fragment-length polymorphism analysis in 134 patients with de novo AML, 34 with therapy-related AML (t-AML), and 178 controls. The distributions of theXRCC3 Thr241Met and NQO1 Pro187Ser genotypes were not significantly different in patients and controls. However, the distribution of the XRCC1 Arg399Gln genotypes was significantly different when comparing the t-AML and control groups (χ2, P = .03). The presence of at least oneXRCC1 399Gln allele indicated a protective effect for the allele in controls compared with patients with t-AML (odds ratio 0.44; 95% confidence interval, 0.20-0.93). We found no interactions between the XRCC1 or XRCC3 and NQO1genotypes. We also found no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes. Our data provide evidence of a protective effect against AML in individuals with at least one copy of the variant XRCC1 399Gln allele compared with those homozygous for the common allele.

-93G>A polymorphism of hMLH1 associated with prognosis for patients with colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4039-4039
Author(s):  
J. Kim ◽  
Y. Chae ◽  
S. Sohn ◽  
B. Kang ◽  
S. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Independent Prognostic Marker ◽  
Dna Repair Capacity ◽  
Pcr Rflp ◽  
Repair Genes

4039 Background: Polymorphisms in the DNA repair genes may contribute to variation in DNA repair capacity, thereby affecting the risk of carcinogenesis and prognosis of colorectal cancer. Accordingly, the present study analyzed polymorphisms of DNA repair genes and their impact on the prognosis for patients with colorectal cancer. Methods: Three hundred and ninety- seven consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of DNA repair genes (XRCC1, hMLH1, ERCC2, ERCC4, VARS2[rs2074511, rs2249459], XPA, XPC, POLR2A, POLR2B, RFC1, RFC4, XAB2, DNMT3B) determined using a PCR-RFLP assay. Results: The median age of the patients was 63 years (range, 21–85), and 218 (54.9%) patients had colon cancer and 179 (45.1%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n=86, 21.7%), stage II (n=146, 36.8%), stage III (n=145, 36.5%), and stage IV (n=20, 5.0%). Multivariate survival analysis including stage, differentiation, age, and CEA level showed that the survival for the patients with the -93AA genotype of hMLH1 was worse than for the patients with the combined -93GG and GA genotype (overall survival: hazard ratio [HR]=2.953, 95% Confidential Interval [CI], 1.273–6.850, P=0.012; disease-free survival: HR=2.299, 95% CI, 1.417–3.730, P=0.001), whereas the other polymorphisms were not associated with survival. Conclusions: The -93G>A polymorphism of hMLH1 was found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, in addition to the pathologic stage, the analysis of -93G>A polymorphism of hMLH1 can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.

scholarly journals 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

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
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.

scholarly journals XRCC1 Arg399Gln Genetic Polymorphism in a Turkish Population

2006 ◽  
Vol 25 (5) ◽  
pp. 419-422 ◽  
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.

scholarly journals Expression of Base Excision DNA Repair Genes Is a Sensitive Biomarker for in Vivo Detection of Chemical-induced Chronic Oxidative Stress

2004 ◽  
Vol 64 (3) ◽  
pp. 1050-1057 ◽  
Author(s):  
Ivan Rusyn ◽  
Shoji Asakura ◽  
Brian Pachkowski ◽  
Blair U. Bradford ◽  
Mikhail F. Denissenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Dna Repair Genes ◽  
In Vivo Detection ◽  
Chronic Oxidative Stress ◽  
Base Excision ◽  
Base Excision Dna Repair ◽  
Repair Genes
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