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)

Triple helix-forming oligonucleotides conjugated to a psoralen (psoTFO) have been designed to bind to three distinct purine-rich sequences within the human interstitial collagenase (MMP1) gene. Gel mobility shift assays indicate that these psoTFO bind to and photoreact with model target DNA sequences following ultraviolet A (UVA) irradiation. The dissociation constants for binding of the psoTFO to their targets range from 0.3 to 4 microM. Psoralen monoadducts with the purine-rich target strand and interstrand crosslinks are efficiently formed on targets containing either 5'-ApT-3' or 5'-TpA-3' sequences adjacent to the TFO binding sequence. The dependence of adduct formation on UVA dose has provided quantitative estimates of the overall rate constants for psoralen monoadduct and crosslink formation in the presence of a TFO. When psoralen is tethered to a TFO, the rate of monoadduct formation exceeds that of crosslinking for all sequences studied. This contrasts with the relatively low rate of monoadduct formation that has been reported for free psoralens, suggesting that the bound TFO facilitates the initial photochemistry that generates monoadducts, but does not significantly affect interstrand crosslink formation. psoTFO and UVA treatment inhibit DNA cleavage by a restriction endonuclease when the psoralen covalently reacts directly at the endonuclease site. The particular TFO studied do not completely inhibit endonuclease activity when they are noncovalently bound or when the covalent psoralen adduct does not coincide with the endonuclease site. Our findings confirm that TFO are capable of directing psoralen photoadducts to specific DNA targets and suggest that TFO can significantly modulate psoralen photoreactivity and DNA-protein interactions.
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PMID:Binding and photoreactivity of psoralen linked to triple helix-forming oligonucleotides. 1098 98

A single guanine insertion (1G/2G polymorphism) in the promoter of the matrix metalloproteinase (MMP-1) gene creates a binding site for the transcription factor and may affect the level of transcription of MMP-1. An elevated level of MMP-1 in cancer cells may facilitate their invasion and contribute to metastasis. To evaluate the contribution of 1G/2G polymorphism in the development and/or progression of breast cancer we genotyped 135 subjects with breast cancer. The 1G/2G polymorphism was determined by the method based on restriction endonuclease digestion. We found that the frequency of the 2G allele was higher in lymphnode-metastasis patients than in the group without metastasis (p < 0.001). We did not find differences between distribution of the genotypes and frequencies of alleles in cancer patients and in healthy subjects served as control. Our results suggest that allele 2G may be associated with lymphnode metastasis in patients with breast cancer and therefore it can be considered as a prognostic marker in this disease.
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PMID:An association between the matrix metalloproteinase 1 promoter gene polymorphism and lymphnode metastasis in breast cancer. 1514 60

A single nucleotide polymorphism in the promoter region of -1607 bp of the human MMP-1 gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis. This study aimed to evaluate the association between the MMP-1 promoter gene polymorphism and chronic periodontitis susceptibility and/or severity in a Chinese population. Genomic DNA was obtained from whole blood samples in 60 Chinese subjects with chronic periodontitis and 50 periodontally healthy subjects as controls. MMP-1 promoter fragment was amplified by polymerase chain reaction, and the polymorphism was analyzed by restriction endonuclease cleavage. In the control subjects, the 2G allele was observed a frequency of 49%, while in severely diseased patients, the 2G allele was seen in 73.4%. The individuals with the 2G allele seem to be approximately three times at greater risk for developing the severe chronic periodontitis (chi(2) = 12.148, P = 0.000). The genotype of 2G/2G was found in 58.5% of the severe periodontitis and 24% of the control group (chi(2) = 11.779, P = 0.003). This study suggests that a single nucleotide polymorphism in the MMP-1 promoter region of -1607 bp may be associated with severe chronic periodontitis in a Chinese population.
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PMID:MMP-1 promoter gene polymorphism and susceptibility to chronic periodontitis in a Chinese population. 1677 38