Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial DNA (mtDNA) is replicated by the DNA polymerase g in concert with accessory proteins such as the mtDNA helicase, single stranded DNA binding protein, topoisomerase, and initiating factors. Nucleotide precursors for mtDNA replication arise from the mitochondrial salvage pathway originating from transport of nucleosides, or alternatively from cytoplasmic reduction of ribonucleotides. Defects in mtDNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mtDNA deletions, point mutations, or depletion which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mtDNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders, such as progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). This review focuses on our current knowledge of genetic defects of mtDNA replication (POLG, POLG2, C10orf2) and nucleotide metabolism (TYMP, TK2, DGOUK, and RRM2B) that cause instability of mtDNA and mitochondrial disease.
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PMID:Defects in mitochondrial DNA replication and human disease. 2217 57

The study aimed to explore the underlying molecular mechanisms of CDK2 inhibition in neuroblastoma by bioinformatics analysis. Gene expression profile GSE16480 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified from IMR32 between each time point and average expression of all time points. Gene significance was calculated using dSVDsig algorithm of dnet package. Protein-protein interaction (PPI) network was built. Then, integrated with gene significance, a core PPI network was detected by dNetPipeline algorithm in dnet package. Finally, pathway enrichment analysis was performed for genes in network. Totally, 1524 DEGs were identified. CCNA2 (cyclin A2), EXO1 (exonuclease 1), RAD51AP1 (RAD51 associated protein 1), TOP2A (topoisomerase (DNA) II alpha) and CDK1 (cyclin-dependent kinase 1) were selected as DEGs with higher connectivity after PPI network analysis. In the network, CCNA2, CDK1, BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) and CCNB1 (cyclin B1) were involved in cell cycle pathway. Additionally, CCNB1, CDK1, CCNE2 (Cyclin E2), and RRM2B (ribonucleotide reductase subunit M2B) were involved in p53 signaling pathway. Cell cycle and p53 signaling pathway were closely associated with neuroblastoma after CDK2 inhibition. The DEGs, such as CCNA2, CCNB1, CDK1 and RRM2B may be the potential targets for neuroblastoma.
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PMID:Microarray expression analysis of MYCN-amplified neuroblastoma cells after inhibition of CDK2. 2825 14