Repair of base–base mismatches in simian and human cells

Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 578-583 ◽  
Author(s):  
Thomas C. Brown ◽  
Josef Jiricny
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
Gene Conversion ◽  
Human Fibroblasts ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Flanking Sequences ◽  
Sv40 Dna ◽  
Derivatives Of ◽  
Genetic Events

Mismatched heteroduplexes arise as intermediates of several dissimilar genetic processes. The outcome of these genetic events will therefore be influenced by the efficiency and specificity of mismatch repair. We have studied the correction of base–base mispairs in simian and human fibroblasts by transfecting the cells with derivatives of SV40 DNA, each harboring a single mispair in a defined orientation. Analysis of plaques revealed that correction efficiencies for homomispairs followed the pattern G∙G > C∙C ≥ A∙A > T∙T. Repair bias was influenced by flanking sequences. Correction efficiencies for heteromispairs followed the pattern of G∙T > A∙C > C∙T > A∙G and repair favored the retention of G+C by a substantial margin. This repair specificity could lead to a gene conversion bias favoring the accumulation of G+C in sequences subject to high levels of recombination or unequal exchange.Key words: DNA repair, gene conversion, recombination, DNA methylation.

scholarly journals XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination.

Genetics ◽  
1992 ◽  
Vol 132 (3) ◽  
pp. 651-664 ◽  
Author(s):  
E L Ivanov ◽  
V G Korolev ◽  
F Fabre
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Gene Conversion ◽  
Meiotic Recombination ◽  
Repair Gene ◽  
Strand Breaks ◽  
Dna Repair Gene ◽  
Mating Type Switching ◽  
Radiation Induced ◽  
Recombination Pathway

Abstract The XRS2 gene of Saccharomyces cerevisiae has been previously identified as a DNA repair gene. In this communication, we show that XRS2 also encodes an essential meiotic function. Spore inviability of xrs2 strains is rescued by a spo13 mutation, but meiotic recombination (both gene conversion and crossing over) is highly depressed in spo13 xrs2 diploids. The xrs2 mutation suppresses spore inviability of a spo13 rad52 strain suggesting that XRS2 acts prior to RAD52 in the meiotic recombination pathway. In agreement with the genetic data, meiosis-specific double-strand breaks at the ARG4 meiotic recombination hotspot are not detected in xrs2 strains. Despite its effects on meiotic recombination, the xrs2 mutation does not prevent mitotic recombination events, including homologous integration of linear DNA, mating-type switching and radiation-induced gene conversion. Moreover, xrs2 strains display a mitotic hyper-rec phenotype. Haploid xrs2 cells fail to carry out G2-repair of gamma-induced lesions, whereas xrs2 diploids are able to perform some diploid-specific repair of these lesions. Meiotic and mitotic phenotypes of xrs2 cells are very similar to those of rad50 cells suggesting that XRS2 is involved in homologous recombination in a way analogous to that of RAD50.

Gap formation is associated with methyl-directed mismatch correction under conditions of restricted DNA synthesis

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 104-111 ◽  
Author(s):  
Shin-San Su ◽  
Michelle Grilley ◽  
Randy Thresher ◽  
Jack Griffith ◽  
Paul Modrich
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Dna Synthesis ◽  
Gene Conversion ◽  
Strand Displacement ◽  
Gap Formation ◽  
Repair Gene ◽  
Mismatch Correction ◽  
Dna Repair Gene ◽  
Gatc Site

A covalently closed, circular heteroduplex containing a G – T mismatch and a single hemimethylated d(GATC) site is subject to efficient methyl-directed mismatch correction in Escherichia coli extracts when repair DNA synthesis is severely restricted by limiting the concentration of exogenously supplied deoxyribonucleoside-5′-triphosphates or by supplementing reactions with chain-terminating 2′,3′-dideoxynucleoside triphosphates. However, repair under these conditions results in formation of a single-strand gap in the region of the molecule containing the mismatch and the d(GATC) site. These findings indicate that repair DNA synthesis required for methyl-directed correction can initiate in the vicinity of the mispair, and they are most consistent with a repair reaction involving 3′ → 5′ excision (or strand displacement) from the d(GATC) site followed by 5′ → 3′ repair DNA synthesis initiating in the vicinity of the mismatch.Key words: DNA repair, gene conversion, mismatch correction, mutagenesis.

scholarly journals DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Aysel Kalayci Yigin ◽  
Mehmet Bulent Vatan ◽  
Ramazan Akdemir ◽  
Muhammed Necati Murat Aksoy ◽  
Mehmet Akif Cakar ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fragment Length Polymorphism ◽  
Control Group ◽  
Chordae Tendineae ◽  
Repair Gene ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Polymerase Chain

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%,p=0.049; 38.15% versus 16.2%,p=0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863;p=0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129;p=0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992;p=0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

scholarly journals DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population

2021 ◽  
Vol 28 (3) ◽  
pp. 1879-1885
Author(s):  
Maria Samara ◽  
Maria Papathanassiou ◽  
Lampros Mitrakas ◽  
George Koukoulis ◽  
Panagiotis J. Vlachostergios ◽  
...  
Keyword(s):  
Dna Repair ◽  
Urothelial Carcinoma ◽  
European Population ◽  
Nucleotide Polymorphisms ◽  
Environmental Carcinogens ◽  
Repair Gene ◽  
High Exposure ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Xrcc3 Thr241met

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

2014 ◽  
Vol 41 (3) ◽  
pp. 458-465 ◽  
Author(s):  
Gustavo Martelli Palomino ◽  
Carmen L. Bassi ◽  
Isabela J. Wastowski ◽  
Danilo J. Xavier ◽  
Yara M. Lucisano-Valim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Systemic Sclerosis ◽  
Blood Cells ◽  
Gene Polymorphisms ◽  
Peripheral Blood Cells ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Repair Genes

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

DNA repair gene XRCC1 polymorphisms in childhood acute lymphoblastic leukemia

2005 ◽  
Vol 217 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Thomas Joseph ◽  
P. Kusumakumary ◽  
Priya Chacko ◽  
Annie Abraham ◽  
M. Radhakrishna Pillai
Keyword(s):  
Dna Repair ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Repair Gene ◽  
Dna Repair Gene
Sign in / Sign up

Export Citation Format

Share Document