The iconic double helical structure of DNA has deep implications in genome biology.
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As DNA molecules are extremely long, they are condensed into chromatin fibers. But, since DNA needs to unfold and unwind during gene transcription and chromosome replication, DNA molecules undergo severe topological constraints (helical twisting, supercoiling, knotting and catenation).
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A ubiquitous class of enzymes, termed topoisomerases, resolve DNA topological problems by producing transient DNA breaks and passing DNA strands throughout each other. Numerous antibiotics and anti-cancer drugs kill cells by interfering the activity of topoisomerases.
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DNA topoisomerases, along with other motor activities that alter chromatin architecture (RNA & DNA polymerases, DNA helicases, remodellers, SMCs complexes), determine where DNA twisting and supercoling shuould be generated or dissipated, and which DNA entanglements must be preserved or eliminated.
Since 1984, I investigate intracellular DNA topology, its regulation and its biological implications. I analyze the occurrence of DNA supercoils, knots and catenanes across eukaryotic chromosomes; the molecular mechanisms that generate, stabilize and dissolve them; and their crucial interplay with genome transactions.
