News from CEXS-UPF
Genetic mutations are changes in the DNA sequence that can cause errors in cell function, and in the worst case, their accumulation leads to serious diseases such as cancer. To avoid this, cells have mechanisms thatare continuously detecting and repairing these changes, but which sometimes fail, resulting in the accumulation of mutations and the emergence of tumours . A scientific team led by Núria López-Bigas, ICREA researcher at the Department of Experimental and Health Sciences (DCEXS) of Pompeu Fabra University (UPF), has found, for the first time, the reason why mutations specifically accumulate in certain regions of the genome in cells of melanoma and lung cancer (adenocarcinoma and lung squamous cell carcinomas), two which are highly prevalent in the population. The results of this research appear published in the latest edition of journal Nature.
The team of López-Bigas has shown that the number of mutations is higher than expected in regions of the DNA to which the so-called transcription factors, proteins that regulate the activity of different genes, are bound. The results of the study indicate that the binding of these proteins to the DNA hinders access to the DNA's repair machinery, which ultimately causes the accumulation of genetic mutations in these areas. Specifically, the analysis of the genomes of 38 melanomas sequenced by The Cancer Genome Atlas consortium, in which the team of Núria López-Bigas is taking part, shows that the mutation rate in these regions is approximately five times higher than in neighboring regions of the genome.
Radhakrishnan Sabarinathan, Loris Mularoni, Jordi Deu-Pons, Abel González-Pérez, Núria López-Bigas. Nucleotide excision repair is impaired by binding of transcription factors to DNA. Nature, April 2016. DOI: 10.1038/nature17661