Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:3.1.30.2 (
endonuclease
)
18,621
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
O(6)-
Methylguanine-DNA methyltransferase
(
MGMT
) is one of the most important DNA-repair enzymes. Herein, a simple, sensitive and selective homogeneous fluorescence assay strategy is developed for the detection of
MGMT
on the basis of target-mediated two consecutive
endonuclease
reactions. The activity assay of
MGMT
is firstly accomplished using a hairpin-structured DNA substrate to offer a specific recognition site on the substrate DNA for restriction
endonuclease
PvuII, and thus to initiate the first
endonuclease
reaction. The product which activates the second
endonuclease
reaction allows an efficient amplification approach to create an abundance of fluorescence signal reporters. The first
endonuclease
reaction offers the method high specificity and the second one furnishes the assay improved sensitivity. The results reveal that the
MGMT
assay strategy shows dynamic responses in the concentration range from 1 to 120 ng mL(-1) with a detection limit of 0.5 ng mL(-1). By simply altering the alkylated bases, this strategy can also be extended for the detection of other alkyltransferases. Therefore, the developed strategy might provide an intrinsically convenient, sensitive and specific platform for alkyltransferase activate assay and related biochemical studies due to its label-free, homogeneous, and fluorescence-based detection format.
...
PMID:Target-mediated consecutive endonuclease reactions for specific and sensitive homogeneous fluorescence assay of O6-methylguanine-DNA methyltransferase. 2426 90
Aberrant promoter methylation of tumor relevant genes frequently occurs in early steps of carcinogenesis and during tumor progression. Epigenetic alterations could be used as potential biomarkers for early detection and for prediction of prognosis and therapy response in lung cancer. The present study quantitatively analyzed the methylation status of known and potential gatekeeper and tumor suppressor genes [
O-6-methylguanine-DNA methyltransferase
(
MGMT
), Ras association domain family member 1A (
RASSF1A
), Ras protein activator like 1 (
RASAL1
), programmed cell death 4 (
PDCD4
), metastasis suppressor 1 (
MTSS1
) and tumor suppressor candidate 3 (
TUSC3
)] in 42 lung cancers and in corresponding non-malignant bronchus and lung tissue using bisulfite-conversion independent methylation-quantification of
endonuclease
-resistant DNA (MethyQESD). Methylation status was associated with clinical and pathological parameters. No methylation was found in the promoter regions of
PDCD4
and
MTSS1
of either compartment.
MGMT
,
RASSF1A
and
RASAL1
showed sporadic (up to 26.2%) promoter methylation. The promoter of
TUSC3
, however, was frequently methylated in the tumor (59.5%), benign bronchus (67.9%) and alveolar lung (31.0%) tissues from each tumor patient. The methylation status of
TUSC3
was significantly associated with smaller tumor size (P=0.008) and a longer overall survival (P=0.013). Pooled blood DNA of healthy individuals did not show any methylation of either gene. Therefore, methylation of
TUSC3
shows prognostic and pathobiological relevance in lung cancer. Furthermore, quantitative detection of
TUSC3
promoter methylation appears to be a promising tool for early detection and prediction of prognosis in lung cancer. However, additional studies are required to confirm this finding.
...
PMID:Quantitative detection of
TUSC3
promoter methylation -a potential biomarker for prognosis in lung cancer. 2769 90
The methylation status of
O-6-methylguanine-DNA methyltransferase
(MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction
endonuclease
digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs) patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04). Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy.
...
PMID:The rs16906252:C>T SNP is not associated with increased overall survival or temozolomide response in a Han-Chinese glioma cohort. 2857 62
