Who's on first in the cellular response to DNA damage?

Key Points Recognition and repair of damaged DNA is essential for genomic stability in all living cells. There are several pathways of DNA repair and, for some types of damage, repair pathways might compete, or alternative pathways might operate. Cellular proteins with other functions might also bind DNA lesions and influence repair. The DNA-damage response is much more than simply the elimination of damage. It also involves the control of when, where and how repair should be accomplished. The ultimate outcome for the cell, and for the organism of which it is a part, might depend on which protein first encounters and binds at the damaged region of DNA. Cellular DNA-repair pathways involve proteins that have roles in other DNA-metabolic processes, as well as those that are dedicated to damage removal. Several proteins, which have diverse functions and are not known to have roles in DNA repair, also associate with damaged DNA. These newly discovered interactions could either facilitate or hinder the recognition of DNA damage, and so they could have important effects on DNA repair and genetic integrity. The outcome for the cell, and ultimately for the organism, might depend on which proteins arrive first at sites of DNA damage.