Functions of Post-Translational Modifications of Key Proteins Involved in DNA Repair – MODDNAREP

The goal of this project is to understand how mammalian cells cope with damage to their genetic material—DNA. If DNA damage is not repaired, it can cause numerous problems for the cell. For example, the cell may not be able to divide when its DNA is damaged because DNA must be free of breaks and lesions to be successfully duplicated. For a normal cell to become cancerous, it must acquire many mutations that alter its genetic program in a way that leads to uncontrolled growth—a hallmark of cancer.

This gradual accumulation of mutations is often accelerated by defective DNA repair mechanisms. The non-homologous end-joining (NHEJ) pathway is essential for DNA repair and is indispensable for organismal survival. We aim to understand how NHEJ is regulated in cells, as this knowledge may enable the development of new anticancer drugs and potentially improve cancer classification and diagnosis. For this reason, we will investigate the post-translational modifications of key NHEJ proteins—PAXX and DNA-PKcs. Post-translational modifications are typically small molecular tags added to already synthesized and functional cellular proteins, which can modulate their activity in various ways. In this project, we seek to determine in detail the functions of post-translational modifications of PAXX and DNA-PKcs.