DNA repair mechanisms are concentrated in the active parts of the genome

Less than 10% of the human genome contains coded information in the form of genes. The 30,000-40,000 genes in the genome are found grouped in discrete regions of the chromosomes. Chemical agents and radiation habitually cause a large variety of injuries to the DNA which interferes in many cell processes, like transcription and replication, and this can cause a loss of control of cell division and the appearance of tumours. In order to avoid this, the human genome contains more than 130 DNA repair genes which are coded by proteins that constantly scrutinise the genome and seek out damage in order to eliminate it.

A team of researchers from the Mutation Group at the Department of Genetics and Microbiology from the Autonomous University of Barcelona, together with investigators from Leiden University Medical Centre in Leiden (Holland), have discovered that the most important part of the human genome, that is to say the zones where the genes are grouped, are subject to a special and preferential control by the repair mechanisms. In this way, the presence of mutations and the appearance of cancer in the most active genes are prevented.

In order to determine how the repair mechanisms act in the whole human genome, the UAB scientists have studied lines of cells derived from the skin of healthy people and from patients deficient in the repair of DNA damage produced by solar radiation, a genetic disorder called xeroderma pigmentosa. In those affected by this disorder (popularised by the characters of the children in the film The Others), the repair mechanisms do not act when ultraviolet light shines on the skin cells, which causes them to have an accumulation of mutations and, therefore, an extremely high incidence of melanoma (skin cancer). The scientists have been able to observe how the repair of damage caused by ultraviolet rays is concentrated in the richest regions of the genome and, therefore, there is preferential repair of the most important part of the genome, called the transcriptome. By way of example, chromosome 19, the densest and most genetically active, shows high levels of repair, whereas in chromosome 4, one of the poorest in genes, there is practically no preferential repair of the mutations induced by ultraviolet light.

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