LIG4 and cancer: Besides ATM and MRE11, defects in other proteins that operate to clear DSBs or replicative stress have been tied to distinct disorders that involve neurological disease, cancer predisposition, and a range of other clinical phenotypes: Nijmegen breakage syndrome 1 (NBS1), ataxia telangiectasia and Rad3-related (ATR), DNA ligase 4 (LIG4), Cernunnos (a.k.a., XLF or NHEJ1), and components of the Fanconi anemia pathway (Table 1).