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The DNA topoisomerases are essential for DNA replication, transcription, recombination, as well as for chromosome compaction and segregation. They may have appeared early during the formation of the modern DNA world. Several families and subfamilies of the two types of DNA topoisomerases (I and II) have been described in the three cellular domains of life (Archaea, Bacteria and Eukarya), as well as...
Candida guilliermondii and human DNA topoisomerases I are inhibited by PL (pyridoxal), PLP (pyridoxal 5′-phosphate) and PLP-AMP (pyridoxal 5′-diphospho-5′-adenosine) (PL<PLP<PLP-AMP).We have recently shown that PLP acted as a competitive inhibitor of C. guilliermondii topoisomerase I, impeding the formation of the cleavable complex from a selective binding to an active site lysine. The targeted...
Mitochondria are the only organelles containing metabolically active DNA besides nuclei. By analogy with the nuclear topoisomerases, mitochondrial topoisomerase activities are probably critical for maintaining the topology of mitochondrial DNA during replication, transcription, and repair. Mitochondrial diseases include a wide range of defects including neurodegeneracies, myopathies, metabolic abnormalities...
Reverse gyrase was discovered more than twenty years ago. Recent biochemical and structural results have greatly enhanced our understanding of their positive supercoiling mechanism. In addition to new biochemical properties, a fine tuning of reverse gyrase regulation in response to DNA damaging agents has been recently described. These data give us a new insight in the cellular role of reverse gyrase...
Microcin B17 (MccB17) is a peptide-based bacterial toxin that targets DNA gyrase, the bacterial enzyme that introduces supercoils into DNA. The site and mode of action of MccB17 on gyrase are unclear. We review what is currently known about MccB17-gyrase interactions and summarise approaches to understanding its mode of action that involve modification of the toxin. We describe experiments in which...
Type IA topoisomerases are enzymes that can modify DNA topology. They form a distinct family of proteins present in all domains of life, from bacteria to archaea and higher eukaryotes. They are composed of two domains: a core domain containing all the conserved motifs involved in the trans-esterification reactions, and a carboxyl-terminal domain that is highly variable in size and sequence. The latter...
The level of negative DNA supercoiling of the Escherichia coli chromosome is tightly regulated in the cell and influences many DNA metabolic processes including DNA replication, transcription, repair and recombination. Gyrase is the only type II topoisomerase able to introduce negative supercoils into DNA, a unique ability that arises from the specialized C-terminal DNA wrapping domain of the GyrA...
DNA transaction events occurring during cell life (replication, transcription, recombination, repair, cell division) are always linked to severe changes in the topological state of the double helix. However, since naked DNA almost does not exist in eukaryote nucleus but rather interacts with various proteins, including ubiquitous histones, these topological changes happen in a chromatin context. This...
DNA is not only a nucleotide sequence which allows the binding of regulators but its intrinsic structural properties such as curvature and flexibility are also viewed as playing an active role in the regulation of transcription. Our combination of computer modelling and AFM imaging allow direct access to DNA curvature and flexibility. We have searched for these DNA structural features involved in...
DNA topoisomerase II is an enzyme that specializes in DNA disentanglement. It catalyzes the interconversion of DNA between different topological states. This event requires the passage of one duplex through another one via a transient double-strand break. Topoisomerase II is able to process any type of DNA, including structures such as DNA juxtapositions (crossovers), DNA hairpins or cruciforms, which...
Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension. Camptothecin and other agents targeting DNA topoisomerase I are used in the treatment of human solid cancers with significant clinical efficacy. Major progress has been achieved in recent years in the understanding of enzyme structures and basic cellular functions of...
The Avi.groEL intron of Azotobacter vinelandii, which interrupts the termination codon of the groEL gene, is shown to belong to a monophyletic subset of bacterial group II introns that share a large insertion at their 5′ extremity and a peculiar genetic localization. Some of these introns are inserted within, right next to, or very close to, a stop codon while others are located immediately 3′ of,...
Local DNA melting is integral to fundamental processes such as replication or transcription. In vivo, these two processes do not occur on molecules free in solution but, instead, involve DNA molecules which are organized into DNA/proteins complexes. Atomic force microscopy imaging offers a possibility to look at individual molecules. It allowed us to follow the progress of local denaturation in liquid,...
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