Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Myc-associated zinc-finger protein, Miz1, activates transcription of the p21cip1 gene in response to UV irradiation. Miz1 associates with topoisomerase II binding protein1 (TopBP1), an essential activator of the Atr kinase. We show here that Miz1 is required for the recruitment of a fraction of TopBP1 to chromatin, for the protection of TopBP1 from proteasomal degradation and for Atr-dependent signal transduction. TopBP1 that is not bound to chromatin is degraded by the HectH9 (Mule, ARF-BP1 and HUWE1) ubiquitin ligase. Myc antagonizes the binding of TopBP1 to Miz1; as a result, expression of Myc leads to dissociation of TopBP1 from chromatin, reduces the amount of total TopBP1 and attenuates Atr-dependent signal transduction. Our data show that Miz1 and Myc affect the activity of the Atr checkpoint through their effect on TopBP1 chromatin association and stability.
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PMID:Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1. 1892 29

During meiosis, DNA double-strand breaks are initiated by the topoisomerase-like enzyme SPO11 and are repaired by inter-sister chromatid and inter-homologue DNA repair pathways. Genome-wide maps of initiating DNA double-strand breaks and inter-homologue repair events are now available for a number of mammalian, fungal and plant species. In mammals, PRDM9 specifies the location of meiotic recombination initiation via recognition of specific DNA sequence motifs by its C2H2 zinc finger array. In fungi and plants, meiotic recombination appears to be initiated less discriminately in accessible chromatin, including at gene promoters. Generally, meiotic crossover is suppressed in highly repetitive genomic regions that are made up of transposable elements (TEs), to prevent deleterious non-allelic homologous recombination events. However, recent and older studies have revealed intriguing relationships between meiotic recombination initiation and repair, and transposable elements. For instance, gene conversion events have been detected in maize centromeric retroelements, mouse MULE-MuDR DNA transposons undergo substantial meiotic recombination initiation, Arabidopsis Helitron TEs are among the hottest of recombination initiation hotspots, and human TE sequences can modify the crossover rate at adjacent PRDM9 motifs in cis. Here, we summarize the relationship between meiotic recombination and TEs, discuss recent insights from highly divergent eukaryotes and highlight outstanding questions in the field.
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PMID:Heterogeneous transposable elements as silencers, enhancers and targets of meiotic recombination. 3133 31