biostudies-literatureUnknown9(9)Petroni MMRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where MCell death & disease895https://www.ebi.ac.uk/biostudies/studies/S-EPMC6117286biostudies-literatureMRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.PMC6117286Petroni MCardinali BBartolazzi AInfante PPetricci ESardina FLocatelli ESahun Roncero MDi Marcotullio LSoddu SGiannini GDi Giulio SCapalbo CBelardinilli FComes Franchini MFabretti FCoppa ATessitore AColicchia VGulino AfalseMRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where M2018-01-01T00:00:00Z2018 Aug2025-04-04T23:34:51.11Z2019-03-26T23:54:10ZS-EPMC61172863016651910.1038/s41419-018-0924-z