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        Untangling a DNA

        replication mystery may

        lead to new antimalarial drugs

        The function of an enzyme, critical to most forms of life, has been revealed.

                          The function of an enzyme, critical to most forms of life, has been revealed. Image:

              research team, led by         “Our study shows that topo VI in plants   and suggests that the enzyme could
              the John Innes Centre         functions to remove chromosome       be a target for anti-malarial drugs
        A ound that the enzyme              tangles that occur during the        in the future. In plants too, topo VI
        DNA topoisomerase VI (topo VI)      endoreduplication process. This      could have potential as a target for
        performs a critical role in removing   potentially explains its presence in   herbicides,” he added.
        chromosome tangles that occur in    plants where during endoreduplication,
        the cell nucleus of plants.         entanglements are most likely to     The next stage for the research
                                            occur,” explains lead author Dr      team is to purify plant and
        This function enables the process of   Shannon McKie.                    plasmodial topo VI enzymes to
        endoreduplication where the DNA                                          characterise their properties and
        content is doubled. Endoreduplication  The team, a collaboration between   develop them as potential drug
        is the source of polyploidy, where   the John Innes Centre and the       targets.
        a plant has multiple sets of        National Institutes of Health, USA,
        chromosomes, including in some      used a combination of biochemistry   Story Source:
        major crops.                        and single-molecule analysis (using   Materials provided by John Innes
                                            magnetic tweezers) to study the      Centre. Note: Content may be
        Topo VI was discovered, many        function of the enzyme in archaea.   edited for style and length.
        years ago, in archaea, a type of
        single-celled organism without      “Our study gives unprecedented insight  Journal Reference:
        a nucleus. It was only found in     into the mechanism of action of this   1. Shannon J McKie, Parth
        plants and parasites such as        enzyme at the molecular level,” said   Desai, Yeonee Seol, Adam MB
        malaria, more recently leading      Group Leader Professor Tony Maxwell   Allen, Anthony Maxwell, Keir C
        to the scientific question: what    and a senior author of the paper.    Neuman. Topoisomerase VI is a
        is the function of this enzyme in                                        chirally-selective, preferential DNA
        eukaryotes, organisms whose cells   “This work may give us a clue to the   decatenase. eLife, 2022; 11 DOI:
        contain a nucleus?                  role of topo VI in plasmodial parasites   10.7554/eLife.67021

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