Role of NEDD8 and neddylation dynamics in DNA damage response

Abstract

Every single cell in human body is suffering ~ 7000 DNA lesions of various types every day. Different kinds of DNA damage response (DDR) are evolved to overcome these threats to maintain genome stability. Failure in the DDR system leads to various diseases ranging from cancer to neurodevelopmental defects. Past years’ studies have unraveled the close relationship between neddylation, an ubiquitin-like modification, and DDR. This functional interplay involves the neddylation of Cullin RING E3 ligases, the prototype neddylation substrates, and non-Cullin-based neddylation targets, both of which have intimate links to DDR. More recently, unconjugated NEDD8 polymers are implicated in DDR as well. Here we summarize these findings to better understand the role that neddylation and deneddylation plays in DDR.