8
Knowledge Corner
Sep 2015
More than 60 years ago, when James Watson and
Francis Crick
1
solved the duplex helical structure of DNA,
the genetic material found in all living organisms, they
predicted that copying DNA requires the separation of the
two complementary strands so each can serve as template
for replication of the other. Ever since, the mechanism and
enzymes involved in the initial melting (destabilization) of
DNA, especially in eukaryotes (organisms including
animals, plants and fungi), have been an outstanding
problem for biologists.
Scientists have already proven that a helicase enzyme
called MCM2-7 is vital for DNA replication. It is believed
that its ring structure is responsible for the initial
destabilization and subsequent separation of duplex DNA.
Solving its structure would provide insights into the
mystery of how the very stable and inert structure of
duplex DNA is disrupted at replication origins during the
initial step of DNA replication. In the past, solving
structures of protein complexes at atomic resolution by
X-ray diffraction requires crystallization of these
complexes. Successful crystallization depends more on
the chances of nature (size, shape, folding, compactness
etc. of individual protein complexes) than skill. As such,
despite years of effort by multiple laboratories,
crystallization of the MCM2-7 complex proved
insurmountable.
The research team led by Prof Bik Tye from the Division
of Life Science at HKUST and Prof Ning Gao at Tsinghua
University succeeded in solving the structure of MCM2-7.
Using state-of-the-art Cryo-electron microscopy
technology with more powerful electron microscopes,
better detectors, faster cameras and more sophisticated
algorithms for image reconstruction, the team solved the
structure of the MCM2-7 complex at a near-atomic
1
Watson, J.D. and Crick, F.H.C. (1953) Molecular structure of nucleic acids.
Nature
:171, 738-739.
By Yuanliang Zhai (IAS Junior Fellow and
Research Assistant Professor of Life Science, HKUST)
Untying
DNA
Knots
