Double duty: ZMYND8 in the DNA damage response and cancer.

Our genetic information is organized into chromatin, which consists of histones and proteins involved in regulating DNA compaction, accessibility and function. Chromatin is decorated by histone modifications, which provide signals that coordinate DNA-based processes including transcription and DNA damage response (DDR) pathways. A major signal involved in these processes is acetylation, which when attached to lysines within proteins, including histones, can be recognized and read by bromodomain-containing proteins. We recently identified the bromodomain protein ZMYND8 (also known as RACK7 and PRKCBP1) as a critical DNA damage response factor involved in regulating transcriptional responses and DNA repair activities at DNA double-strand breaks. Other studies have further defined the molecular details for how ZMYND8 interacts with chromatin and other chromatin modifying proteins to exert its DNA damage response functions. ZMYND8 also plays essential roles in regulating transcription during normal cellular growth, perturbation of which promotes cellular processes involved in cancer initiation and progression. In addition to acetylation, histone methylation and demethylase enzymes have emerged as important regulators of ZMYND8. Here we discuss our current understanding of the molecular mechanisms that govern ZMYND8 function within chromatin, highlighting the importance of this protein for genome maintenance both during the DDR and in cancer.