In this review, we discuss a novel on-site remodeling function that is mediated 
by the H2A-ubiquitin binding protein ZRF1. ZRF1 facilitates the remodeling of 
multiprotein complexes at chromatin and lies at the heart of signaling processes 
that occur at DNA damage sites and during transcriptional activation. In 
nucleotide excision repair ZRF1 remodels E3 ubiquitin ligase complexes at the 
damage site. During embryonic stem cell differentiation, it contributes to 
retinoic acid-mediated gene activation by altering the subunit composition of 
the Mediator complex. We postulate that ZRF1 operates in conjunction with 
cellular remodeling machines and suggest that on-site remodeling might be a 
hallmark of many chromatin-associated signaling pathways. We discuss yet 
unexplored functions of ZRF1-mediated remodeling in replication and double 
strand break repair. In conclusion, we postulate that on-site remodeling of 
multiprotein complexes is essential for the timing of chromatin signaling 
processes.