EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele

摘要: The maintenance of genome stability is critical for the suppression diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. DNA damage response (DDR) orchestrates appropriate cellular responses following detection lesions prevent genomic instability. MRE11 complex a sensor double strand breaks (DSBs) plays key roles in multiple aspects DDR, including end resection signaling repair. has been shown function both upstream concert with 5'-3' exonuclease EXO1 resection, but it remains unclear what extent influences DSB independently complex. Here we examine genetic relationship during mammalian development damage. Deletion Exo1 mice expressing hypomorphic allele Nbs1 leads severe impairment, embryonic death chromosomal While minimal role normal cells, its loss strongly replication, repair, checkpoint sensitivity NBS1 cells. Collectively, our results establish modulating severity mutations.