Monday, January 16, 2012

Repair centers protect DNA against radiation

Cells contain several mechanisms to prevent our genetic code from changing or getting damaged. It is possible to break down DNA, by exposing it to radiation. Scientists from the University of California have discovered that so-called repair centers are formed, in which broken parts of genetic code are being repaired. It lead them to believe that radiation at lower doses is not as dangerous as we assume.

RIF
Radiation can cause the bonds between individual pieces of code, called nucleotides, to break down. Nucleotides come in four varieties, A, T, C and G. In our genome, an A is paired with T, and C is paired with G. If the DNA breaks down on both sides of the pairs, the nucleotides need to be re-attached. This is known as a double strand break, because DNA consists of two strands entwined with each other. We have special molecules capable of sensing damage. They all move to the damage site, whereafter they can be seen under the microscope, as something described as "radiation induced foci" (RIF). If the amount of DNA damage increases, more RIF are needed. In their experiments, the scientists found that RIF does not increase linearly with dose: a higher dose yields less RIF, which obviously makes higher doses of radiation more harmful in terms of the destruction of genetic material.
Many molecules are involved with DNA breaks. It eventually leads to cell cycle arrest, which means the cell can not progress in growth until the damage is repaired.
Repair centres
RIF's have been discovered a long time ago. The Californian scientists revealed, however, that double-stranded breaks in the DNA cluster together. In combination with repair molecules found in the RIF, a repair centre is formed. Apparently, the molecules work together to fix multiple breaks at once. We do not know much about these centres, though it is apparent that it forms under the influence of DNA damage and is aimed at efficiently resolving the problems.

Mutations
Genetic cross-over.
Repairing DNA breaks is of the utmost importance. If the problems are not swiftly resolved, the loose ends could be attached to other parts of the genome, and thereby resulting in a genetic cross-over. Our DNA is wound up in several packages, known as chromosomes. When double strand breaks make DNA detach from the chromosome they belong to, it can become rearranged in various ways. The picture on the right gives an example of this form of cross-over. It is known that these genetic mutations can cause cancer, which also explains the high incidence of tumours after nuclear disasters such as Chernobyl.

Radiation
It was already known that the body can not cope with the severity of the DNA-damaging effects of radiation when exposed to high doses. We have carved our guidelines on how much radiation a human can withstand from damage reports on people exposed to high levels, for example after a nuclear disaster. It is of course not ethical to expose people to low doses of radiation and assess when they start to develop tumours. We have assumed that the formation of RIF is linear with dose. However, the Californian scientists have shown non-linearity. Because RIF are relatively much higher in low doses compared to high doses, we ought to withstand low radiation levels better than originally thought. Studying how our body exactly forms repair centres from RIF, and how we can increase them will be relevant to assess more accurately what effect radiation in lower doses has on our body. We may also be able to manipulate it to more effectively repair DNA damage.

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