Fig. 8: Proposed model for AATF promoted NHEJ repair in GSCs.

Prior to DNA damage, AATF forms a complex with XRCC4; Upon DNA damage, ATM interacts with and phosphorylates AATF at its Ser189 residue, which drives AATF-XRCC4 complex dissociation, thereby allowing rapid recruitment of XRCC4 to DSB sites to drive NHEJ repair (left). Knockdown of AATF results in polyubiquitination and subsequent proteasomal degradation of XRCC4, thus inhibiting NHEJ repair (middle). The non-phosphorylatable AATF mutant variant blocks recruitment of XRCC4 to DSB sites and inhibits NHEJ repair (right).