DNA double-strand-breaks (DSBs) are the most serious DNA damage, which can be repaired mainly by two pathways, namely homologous recombination repair (HR) and non-homologous-end-joining (NHEJ).Failure to repair DSBs can lead to genome instability which is fimdamentally important in senescence in all eukaryotes.XLF (XRCC4-1 ike factor) is a newly identified NHEJ protein, whose loss-of-function mutations result in human immunodeficiency with microcephaly.