Untangling a DNA replication mystery may lead to new antimalarial drugs
Date:
February 2, 2022
Source:
John Innes Centre
Summary:
The function of an enzyme, critical to most forms of life, has
been revealed.
FULL STORY ==========================================================================
The function of an enzyme, critical to most forms of life, has been
revealed.
==========================================================================
A research team, led by the John Innes Centre found that the enzyme
DNA topoisomerase VI (topo VI) performs a critical role in removing
chromosome tangles that occur in the cell nucleus of plants.
This function enables the process of endoreduplication where the DNA
content is doubled. Endoreduplication is the source of polyploidy, where
a plant has multiple sets of chromosomes, including in some major crops.
Topo VI was discovered, many years ago, in archaea, a type of
single-celled organism without a nucleus. It was only found in plants
and parasites such as malaria, more recently leading to the scientific question: what is the function of this enzyme in eukaryotes, organisms
whose cells contain a nucleus? "Our study shows that topo VI in
plants functions to remove chromosome tangles that occur during the endoreduplication process. This potentially explains its presence in
plants where during endoreduplication, entanglements are most likely to
occur," explains lead author Dr Shannon McKie.
The team, a collaboration between the John Innes Centre and the National Institutes of Health, USA, used a combination of biochemistry and single- molecule analysis (using magnetic tweezers) to study the function of
the enzyme in archaea.
"Our study gives unprecedented insight into the mechanism of action of
this enzyme at the molecular level," said Group Leader Professor Tony
Maxwell and a senior author of the paper.
"This work may give us a clue to the role of topo VI in plasmodial
parasites and suggests that the enzyme could be a target for anti-malarial drugs in the future. In plants too, topo VI could have potential as a
target for herbicides," he added.
The next stage for the research team is to purify plant and plasmodial
topo VI enzymes to characterise their properties and develop them as
potential drug targets.
========================================================================== Story Source: Materials provided by John_Innes_Centre. Note: Content
may be edited for style and length.
========================================================================== Journal Reference:
1. Shannon J McKie, Parth Desai, Yeonee Seol, Adam MB Allen, Anthony
Maxwell, Keir C Neuman. Topoisomerase VI is a chirally-selective,
preferential DNA decatenase. eLife, 2022; 11 DOI:
10.7554/eLife.67021 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/02/220202111811.htm
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