Dynamics of DNA repair proteins at nucleosomes – DYPROSOME

We propose a combined computational and experimental study of the molecular mechanisms by which repair proteins identify the earliest stages of DNA damage in chromatin. DNA damage repair processes (DDR) are tightly regulated among several pathways operating for different types of damage. However, the very early stages of DDR are still little explored on a molecular level, since this requires advanced computational and experimental techniques that are only now developing. How do proteins can initially identify damaged DNA regions? Which molecular interactions direct repair to one pathway with respect to another, for a given type of damage? To what extent does the variable degree of compaction of nucleosomes affect the access of repair proteins to damaged DNA? We will focus on DNA lesions localized at nucleosomes, the key compaction units in chromatin structure, and study their interaction with a carefully chosen set of proteins operating at the very early stages of the repair chain.