News from CRG and CEXS-UPF
All our cells require the small molecule; ATP, generated in the mitochondria to cover the energy required for cell metabolism, dynamics and growth. To a lower extent and particularly in cancer cells, ATP can also be generated in the cytoplasm from the energy gained during degradation of glucose. These sources of ATP are sufficient to cover the energetic needs of cells in normal conditions. However, in response to stress-inducing external signals or to extensive DNA damage, the cells need to globally reprogram their gene expression pattern, a process that requires extensive remodelling of chromatin to gain access to the regulatory information encoded in DNA.
The DNA in the cell nucleus is packaged into chromatin in a form that prevents access to genetic information. Global reprogramming of gene expression to deal with stressful situations and high levels of DNA damage requires loosening the interaction of DNA with chromatin proteins. The modification of chromatin proteins consumes large amounts of energy. To cover these special needs, the cells require an extra amount of energy so, a new pathway is activated in order to get more ATP available.
In a paper published on 3rd June in Science, researchers at the CRG led by senior group leader Miguel Beato in collaboration with the UPF, the Institute for Biomedical Research in Barcelona, and the University Rovira i Virgili in Tarragona, Spain, have described for the first time a new pathway generating energy within the cell nucleus for remodelling chromatin and reprogramming gene expression. They have also identified the function of enzymes involved at every step of this process and how they are activated in response to stress signals. Their results, will help in understanding the mechanisms underlying chromatin remodelling, its relationship with DNA damage and, by extension, with cancer.
Wright R et al. ‘ADP-ribose derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodelling’ Science. 3 June 2106.