Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The helicases XPB and XPD are part of the TFIIH complex, which mediates transcription initiation as well as eukaryotic nucleotide excision repair (NER). Although there is no TFIIH complex present in archaea, most species contain both XPB and XPD and serve as a model for their eukaryotic homologs. Recently, a novel binding partner for XPB, Bax1 (binds archeal XPB), was identified in archaea. To gain insights into its role in NER, Bax1 from Thermoplasma acidophilum was characterized. We identified Bax1 as a novel Mg(2+)-dependent structure-specific endonuclease recognizing DNA containing a 3' overhang. Incision assays conducted with DNA substrates providing different lengths of the 3' overhang indicate that Bax1 specifically incises DNA in the single-stranded region of the 3' overhang 4-6 nucleotides to the single-stranded DNA/double-stranded DNA junction and thus is a structure-specific and not a sequence-specific endonuclease. In contrast, no incision was detected in the presence of a 5' overhang, double-stranded DNA, or DNA containing few unpaired nucleotides forming a bubble. Several Bax1 variants were generated based on multiple sequence alignments and examined with respect to their ability to perform the incision reaction. Residues Glu-124, Asp-132, Tyr-152, and Glu-155 show a dramatic reduction in incision activity, indicating a pivotal role in catalysis. Interestingly, Bax1 does not exhibit any incision activity in the presence of XPB, thus suggesting a role in NER in which the endonuclease activity is tightly regulated until the damage has been recognized and verified prior to the incision event.
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PMID:Bax1 is a novel endonuclease: implications for archaeal nucleotide excision repair. 1975 13

Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of atherosclerosis. Genetic research on coronary artery disease (CAD) has traditionally focused on investigation aimed at identifying disease-susceptibility genes. The aim of this study was to investigate the relationship between AP-endonuclease-1 (Asp148Glu), XRCC1 (Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), XPG (Asp1104His), and hOGG1 (Ser326Cys), gene polymorphisms and the risk of developing CAD in a Turkish population. The study population consisted of 197 patients with acute coronary syndrome (ACS) with chronic CAD and 135 healthy subjects' age and sex matched. Gene polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism method. We demonstrated for the first time, a positive association of XRCC3 and hOGG1 DNA repair gene variants with CAD risk. XRCC3 Thr/Thr genotype and Thr allele frequencies were significantly increased in ACS and chronic CAD patients compared with the control group (p<0.05). It was also observed that there is a protective role of XRCC3 Met alleles against both ACS and chronic CAD (p<0.05). hOGG1 Cys alleles were found significantly higher in ACS patients than in the control group and carriers of the Cys allele had a 1.7-fold increased risk for ACS. In addition, we confirmed the association of XRCC3 Thr241Met and hOGG1 Ser326Cys gene variants with CAD by haplotype analysis. We found that CAD risk is associated with XRCC3 Thr: hOGG1 Cys haplotype, whereas XRCC3 Met: hOGG1 Ser haplotype was found to be protective against the disease. The preliminary results suggested that XRCC3 and hOGG1 genetic variants may be risk factors by affecting the enzyme's function that may lead to development of CAD.
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PMID:Association between genetic variants of DNA repair genes and coronary artery disease. 2336 30

Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a "copy-and-paste" mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3' DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway. To determine if the NER pathway prevents the insertion of retroelements in the genome, we monitored the retrotransposition efficiencies of engineered L1 elements in NER-deficient cells and in their complemented versions. Core proteins of the NER pathway, XPD and XPA, and the lesion binding protein, XPC, are involved in limiting L1 retrotransposition. In addition, sequence analysis of recovered de novo L1 inserts and their genomic locations in NER-deficient cells demonstrated the presence of abnormally large duplications at the site of insertion, suggesting that NER proteins may also play a role in the normal L1 insertion process. Here, we propose new functions for the NER pathway in the maintenance of genome integrity: limitation of insertional mutations caused by retrotransposons and the prevention of potentially mutagenic large genomic duplications at the site of retrotransposon insertion events.
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PMID:The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition. 2804 4


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