Tuesday, January 08, 2008

Scientists capture vital DNA images during cell division

Houston, Jan 8 - Researchers have for the first
time captured detailed images of life's essence and revealed
the structure of a DNA-protein complex that is crucial in the
spread of antibiotic resistance among bacteria.
The dazzling pictures reveal a key step in the process
of cell division, which all organisms must undergo to survive.
The moment occurs deep within a cell, as two proteins work in
concert to unzip a strand of DNA to create two new cells.
Until now, scientists seeking to directly observe this
essential process could only view fuzzy images taken by an
electron microscope.
A scientist at the University of Texas M.D. Anderson
Cancer Center has changed that by perfecting a technique
employed by biophysicist Rosalind Franklin more than half a
century ago to gather the first images of DNA.
The research focuses on how DNA separates and maintains
its integrity when a cell divides. Using X-ray
crystallography, the team led by structural biologists Maria
Schumacher, with colleagues at the University of Sydney,
Australia, produced clear 3-D images of the structure that
results when two proteins connect with a DNA site to
"segregate" DNA during cell division.
"We solve structures to answer questions about how
molecules carry out their biological functions. Without
knowing the structure, you can't understand molecular
mechanisms at a detailed level," says Schumacher, associate
professor.
In this case, Schumacher and colleagues answer a basic
science question and flag a possible target for clinical
attack on antibiotic-resistant Staphlococcus Aureas, a
tenacious and often lethal staph infection.


By understanding the precise mechanism by which a cancer
cell divides, for instance, it might be possible for
scientists to develop a better drug to stop the process.
"The plasmid segregation system we are working on,
called pSK41, is found in S. aureus and confers resistance to
multiple antibiotics, including the drug of last resort,
vancomycin," Schumacher says.
"Because the segregation systems are essential for the
retention of these multidrug resistant plasmids, they
represent wonderful drug targets."
Plasmids are additional strips or circles of DNA found
in bacteria that provide the bacterium with some mechanism of
defence -- in this case, protection against antibiotics.
Plasmids can be transferred from one type of bacteria
to another through a number of mechanisms.
Plasmids are also a great model for understanding cell
division and segregation, Schumacher says, because plasmid
segregation is relatively simple: two proteins connect to one
DNA site to launch the process. Cells divide to multiply and
it's crucial for this split to go smoothly so each daughter
cell ends up with the DNA it needs to function.
"If these plasmids don't divide and go to the next
generation of cells, those bacteria cells lose their drug
resistance," Schumacher notes.
In the Nature paper, the scientists capture the first
structure ever solved of a segrosome complex that partitions
and divides DNA.
A protein called ParR connects with a centromere DNA
site, a round string of DNA repeats in the plasmid, to form
the segrosome complex, which then completes itself by
attracting filaments of another protein called ParM.

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