Roles of ZRANB3 in replication stress response

The maintenance of complete and undamaged genome is critical for survival. However, genomic stability is continually challenged by various assaults from the endogenous and exogenous sources. One of the major threats to genome stability is the “replication stress”, caused by events that impede smooth progression of DNA replication. Cellular responses to replication stress involve PCNA, a processivity factor for eukaryotic DNA polymerases. PCNA interacts with an impressive collection of various protein factors, among which are structure-specific nucleases. We investigated the roles of an unusual endonuclease ZRANB3 at the cellular, biochemical and structural level. Our data provide new molecular insights into the replication stress response and suggest a functional link between ZRANB3 and cancer.