Crosstalk between cellular metabolism and DNA repair

The maintenance of genetic information is required to suppress diseases, including cancer and rare diseases. To do so cells have a complex signaling network that detects DNA damage and subsequently repairs it. This network relies on the cells chemical state, or metabolism, and hence alterations in cellular metabolism can impact DNA damage and repair. However, while there are a few examples highlighting the interplay between metabolism and DNA repair, this has not be studied systematically. We propose that current technologies including gene editing (using CRISPR-Cas9) and chemical biology (with the development of inhibitor compounds) now allow for such systematic investigations. Hence, using these technologies along with markers for DNA damage, we propose to research how metabolic processes affect DNA damage and repair. Having identified novel interactions we will next study how they function at the molecular level. This study will lead to an understanding of how the cells chemical state affects the fundamental cellular process of DNA repair that is ultimately necessary to safeguard genomic information. Therefore, we will gain insight into diseases associated with DNA repair deficiencies that could lead to better treatments.

Maintaining human genomes is required to suppress diseases, including cancer and rare diseases. To do so cells have a complex signaling network that detects any damage that might occur to DNA, that makes up our genomes. This network can repair this damage and relies on the cells' chemical state, or metabolism, and hence alterations in cellular metabolism can impact DNA damage and repair. While there are a few examples highlighting how metabolism can affect DNA repair, this has not be studied systematically. We propose that current technologies including gene editing (using CRISPR-Cas9) and chemical biology (with the development of inhibitor compounds) now allow for such systematic investigations. Hence, using these technologies along with markers for DNA damage, we have researched how metabolic processes affect DNA damage and repair. Having identified novel interactions we have studied how they function at the molecular level. Our findings have increased our understanding of how the cells chemical state affects the fundamental cellular process of DNA repair that is ultimately necessary to safeguard genomic information. This means we have better understood how diseases associated with DNA repair deficiencies occur and so ultimately these findings could lead to better treatments for diseases associated with genome instability.