Isoform 4: Cell-cycle-specific inhibitor of classical non-homologous end joining (NHEJ) of DNA double-strand break (DSB) repair during the S and G2 phases (PubMed:24610814, PubMed:28959974). Acts as a regulator of DNA repair pathway choice by specifically inhibiting classical NHEJ during the S and G2 phases, thereby promoting error-free repair by homologous recombination during cell cycle phases when sister chromatids are present (PubMed:28959974). Preferentially protects single-stranded overhangs at break sites by inhibiting classical NHEJ, thereby creating a local environment that favors homologous recombination (PubMed:28959974). Acts via interaction with XRCC5/Ku80 and XRCC6/Ku70, interaction restricted during the S and G2 phases only (PubMed:28959974). Molecular mechanisms governing classical NHEJ inhibition via interaction with XRCC5/Ku80 and XRCC6/Ku70 are unknown (PubMed:28959974).