IN THE intricately choreographed process of cell division, strips of DNA
called centromeres, where dividing chromosomes split, play a vital part. Now
researchers have shown that other DNA sequences can somehow learn the
centromere鈥檚 dance. This may help scientists create artificial chromosomes for
use in gene therapy.
Gary Karpen and his colleagues at the Salk Institute in La Jolla, California,
witnessed a tiny piece of a fruit fly chromosome breaking off and growing a new
centromere that allows the fragment to be copied like a minichromosome. In the
past, doctors have come across rare cases of minichromosomes in patients, but
the origin of newly sprouted centromeres remained a mystery.
Normally, before a cell divides, each chromosome is copied and the pairs line
up in the cell鈥檚 centre. Protein fibres from each end of the cell grab the
chromosomes at the centromere. The two chromosome copies then break apart and
move along the fibres to opposite sides of the cell, which splits down the
middle.
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Many researchers believed that the key to the centromere鈥檚 function was that
it always had the same characteristic DNA sequence. But it turned out that the
sequence varies widely鈥攏ot only between species but also between a single
organism鈥檚 chromosomes.
To find out more about how the centromere works, Karpen鈥檚 team irradiated a
fruit fly X chromosome to break it apart and rearrange it so that the centromere
was close to one end. Further irradiation broke off a tiny piece of the tip,
only about 0.05 per cent of the whole chromosome, leaving the normal centromere
behind.
Remarkably, a copy of the tip was reliably passed on to daughter cells. 鈥淭hat
tip was surprisingly transmittable through cell division,鈥� Karpen says. Several
tests suggested that it must have 鈥渟prouted鈥� its own centromere, his team
reports in this month鈥檚 Nature Genetics (vol 18, p 30).
Karpen suspects that the DNA tip developed a centromere because it had been moved close
to a centromere on the X chromosome. A factor from the centromere may possibly
spread out over nearby DNA, which can then be retained, making the DNA function
like a centromere when it is isolated.
Alternatively, other DNA might contain dormant centromeres that are 鈥渟witched
off鈥� by the working one. When the DNA is snipped off and the inhibition stops,
the dormant centromere goes into action. But Karpen thinks this idea is less
likely. 鈥淚f you cut the normal end of X off, it does not act like that,鈥� he
points out.
鈥淚t鈥檚 quite a big change in the way that people are thinking about the
centromere,鈥� says Chris Tyler-Smith of Oxford University, who also studies
centromeres. If scientists can confirm what induces normal DNA to take on the
centromere鈥檚 task, this may lead to artificial human chromosomes that can
replicate fast enough to be practical in gene therapy.
