9
Sep 2015
Knowledge Corner
Overall structure of the MCM2-7 (in color)
and model for initial origin melting (MCM2-7
complex in grey, DNA in black).
The left figure shows how each subunit of MCM2-7 form
constriction points to immobilize DNA for deformation.
The right figure illustrates how the staggered rings
provide tight fitting for helical DNA.
The research team members, Dr Yuanliang Zhai (right), IAS Junior
Fellow and Research Assistant Professor and Prof Bik Tye, Visiting
Professor are both from the Division of Life Science at HKUST.
resolution of 3.8Å, which is five times higher than the
best reported structure.
The most striking feature found from the research is that
the two rings of a MCM2-7 complex form a tilted and
twisted dimer through their N-terminal domain. The
central channel, formed by these two staggered rings,
has four constriction points that would restrict the
movement of duplex DNA with tight grips and a kink at
the interface of the two rings that would deform the
bound DNA. This fine structure instructs the function
of the MCM2-7 complex in DNA melting. First, the
deformed DNA at the kinked interface of the two rings
would serve as a nucleation center for DNA
destabilization. Second, the tight grip of duplex DNA
at either end by each hexamer would further deform
DNA at the nucleation point if rotated against each
other. Third, possible rotations between ring structures
formed by subdomains of each hexamer would lower
the activation energy for DNA destabilization even
further. This model proposed that allosteric
conformational changes following the activation of the
MCM2-7 complex by cell cycle regulated kinases
bring about DNA destabilization. These findings are
published in Nature in July 2015 and important
lessons learned from this study are highlighted in the
“News and Views” of the same issue.
Another research project on DNA initiated by Dr Zhai, Prof Tye and Prof Guang Zhu (LIFS, HKUST) has been granted funding by the Research Grants Committee.
For details, please read “Championing Research @ IAS” on P.12.
