Nbn and Atm Cooperate in a Tissue and Developmental Stage-Specific Manner to Prevent Double Strand Breaks and Apoptosis in Developing Brain and Eye

摘要: Nibrin (NBN or NBS1) and ATM are key factors for DNA Double Strand Break (DSB) signaling repair. Mutations in NBN result Nijmegen Breakage Syndrome Ataxia telangiectasia. These syndromes share common features such as radiosensitivity, neurological developmental defects cancer predisposition. However, the functional synergy of Nbn Atm different tissues stages is not yet understood. Here, we show vivo consequences conditional inactivation both genes neural stem/progenitor cells using Nestin-Cre mice. Genetic central nervous system Nbn-deficient mice led to reduced life span increased DSBs, resulting apoptosis during development. Surprisingly, increase DSBs was found only few including cerebellum, ganglionic eminences lens. In sharp contrast, showed that associated with deletion prevented by simultaneous developing retina. Therefore, propose collaborate prevent DSB accumulation development a tissue- stage-specific manner.