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A closer look at DNA's loose ends
A chromosome translocation is visualized in living cells by the colocalization of chromosome breaks marked with differently colored fluorescent proteins (green, red).
[Image courtesy of Vassilis Roukos]
A new study published in the journal Science provides a first look at the events leading to rips and tears in our DNA. The particular method the study used also suggests a way to monitor DNA breaks in real time.
Human cells experience DNA damage regularly, both as a result of normal cellular activity and from environmental factors outside the body, such as radiation. Consequently, the DNA repair process is always on, correcting DNA structure.
If normal DNA repair fails, however, permanent damage can occur to the host cell. One example of this is when both strands of DNA's double helix are broken, in what is called a double-strand break (DSB). A DSB is particularly hazardous to a cell because, when one broken strand tries to pair up again without a healthy strand as a guide, it can wander off and pair to a different chromosome. This results in the rearrangement of the genes, which can cause harmful mutations.
This problematic pairing, called a chromosome translocation, happens regularly in cancer cells. Despite the frequency of chromosome translocations, however, not much is understood about events that cause them. Now, Vassilis Roukos from the National Cancer Institute and colleagues have developed a system to monitor their occurrence in real time.
In the lab, the researchers captured the movements of tiny components of human cells using a very detailed imaging technique called ultrahigh-throughput time-lapse imaging. Doing this, they identified very rare translocation events, including double-strand breaks, as they occurred.
Based on their findings, Roukos and colleagues were able to characterize several aspects of the way translocations occur in space and time. For example, translocations typically form within hours of the occurrence of double-strand breaks. They also form independently of the cell cycle phase, the researchers discovered.
The work of Roukos and colleagues, providing the first in vitro look of chromosome translocations in living cells, suggests an experimental system that could one day be used to study these potentially damaging events in vivo.