Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

ABSTRACT: Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an ev

SUBMITTER: Kumar S 

PROVIDER: S-EPMC5520492 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature