Research led by Francis Crick Institute scientists gives
important insights into how the machinery that copies DNA
functions, heralding further research aimed at intervening when the
process goes awry.
Dr Alessandro Costa of the Francis Crick Institute (currently
based at Clare
Hall laboratories) said: "Making accurate copies of DNA is
essential to maintain the physical integrity of our chromosomes and
avoid the onset of cancer."
Dr Costa's team used high-resolution cryo-electron microscopy to
obtain the structure of an enzyme called helicase, imaged as it
moves along DNA.
They combined this 3D structure with single-molecule
fluorescence imaging (in collaboration with David Rueda's group at
Imperial College London), to investigate how DNA is manipulated as
the helicase engages it.
This showed that the helicase moves on one single DNA filament
and pushes away the other filament, hence unzipping the double
helix.
Dr Costa said: "Helicases work just like motors, burning fuel to
provide motive power. We explain how fuel combustion in the
helicase produces movement that makes the replication machinery
advance on the DNA during replication. By understanding how this
molecular machine works we can learn how to intervene when things
go wrong."
"Our study will enable cancer biologists to ask new important
questions. For example, how can the DNA replication machinery halt
to facilitate DNA repair when a damaged site is encountered
on the double helix? This is a fundamental process that
prevents the accumulation of breakages in our chromosomes, a
frequent cause of cancer."
The paper, Cryo-EM structures of the eukaryotic replicative helicase bound to
a translocation substrate, is published in Nature
Communications.