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)

Transient global or focal ischemia leads to the production of several types of lesions in the DNA backbone including alkali-labile sites, and both single-stranded (ss) and double-stranded (ds) breaks. The ds breaks result in high molecular weight fragments of 10-50 kbp that contain both 3'- and 5'-OH end-groups, suggesting that more than one endonuclease is involved. This lesioning of DNA is followed by the appearance of the damage-response indicator Gadd45 in the ischemic hemisphere following middle cerebral artery occlusion. By 6 h, gadd45 mRNA was shown to increase by semi-quantitative reverse transcriptase - polymerase chain reaction. In situ hybridization histochemistry indicated that these increases in gadd45 mRNA occurred in pyramidal neurons located on the edge of the infarcted cortex. Gadd45 immunostaining yielded similar findings with maximal protein staining detected at 18 h after occlusion. In neurons, in the infarct core with frank DNA fragmentation shown by in situ TdT-mediated dUTP-biotin nick end labeling (TUNEL) at 24 h, the Gadd45 immunostaining was not visible. Taken together, these findings suggest that Gadd45 responds to DNA damage following ischemia as part of a repair response mounted by brain cells attempting to survive the insult.
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PMID:Increases in DNA lesions and the DNA damage indicator Gadd45 following transient cerebral ischemia. 949 61

DNA methylation is an epigenetic modification that is essential for gene silencing and genome stability in many organisms. Although methyltransferases that promote DNA methylation are well characterized, the molecular mechanism underlying active DNA demethylation is poorly understood and controversial. Here we show that Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha), a nuclear protein involved in maintenance of genomic stability, DNA repair and suppression of cell growth, has a key role in active DNA demethylation. Gadd45a overexpression activates methylation-silenced reporter plasmids and promotes global DNA demethylation. Gadd45a knockdown silences gene expression and leads to DNA hypermethylation. During active demethylation of oct4 in Xenopus laevis oocytes, Gadd45a is specifically recruited to the site of demethylation. Active demethylation occurs by DNA repair and Gadd45a interacts with and requires the DNA repair endonuclease XPG. We conclude that Gadd45a relieves epigenetic gene silencing by promoting DNA repair, which erases methylation marks.
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PMID:Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. 1726 71