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SPECIALITY



        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: www.jic.ac.uk


              research team, led by the      “Our study shows that topo VI in    role of topo VI in plasmodial para-
              John Innes Centre found        plants functions to remove chromo-  sites and suggests that the enzyme
              t
        A hat the enzyme DNA to-             some tangles that occur during the   could be a target for anti-malarial
        poisomerase VI (topo VI) performs    endoreduplication process. This     drugs in the future. In plants too,
        a critical role in removing chromo-  potentially explains its presence in   topo VI could have potential as a
        some tangles that occur in the cell   plants where during endoreduplica-  target for herbicides,” he added.
        nucleus of plants.                   tion, entanglements are most likely
                                             to occur,” explains lead author Dr   The next stage for the research
        This function enables the process    Shannon McKie.                      team is to purify plant and plasmo-
        of endoreduplication where the                                           dial topo VI enzymes to charac-
        DNA content is doubled. Endoredu-    The team, a collaboration between   terise their properties and develop
        plication is the source of polyploidy,   the John Innes Centre and the   them as potential drug targets.
        where 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 edit-
        Topo VI was discovered, many         function of the enzyme in archaea.  ed for style and length.
        years ago, in archaea, a type of
        single-celled organism without       “Our study gives unprecedented      Journal Reference:
        a nucleus. It was only found in      insight into the mechanism of action   1. Shannon J McKie, Parth Desai,
        plants and parasites such as         of this enzyme at the molecular     Yeonee Seol, Adam MB Allen,
        malaria, more recently leading to    level,” said Group Leader Professor   Anthony Maxwell, Keir C Neuman.
        the scientific question: what is the   Tony Maxwell and a senior author   Topoisomerase VI is a chirally-se-
        function of this enzyme in eu-       of the paper.                       lective, preferential DNA decate-
        karyotes, organisms whose cells                                          nase. eLife, 2022; 11 DOI: 10.7554/
        contain a nucleus?                   “This work may give us a clue to the   eLife.67021



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