Which DNA repair pathway is activated by ATM after detecting double-strand breaks?
Double-strand breaks present challenging repair choice between rapid but error-prone non-homologous end joining and accurate homologous recombination available only when sister chromatid present. ATM kinase activated by MRN complex phosphorylates H2AX, creating gamma-H2AX domains that recruit mediator 53BP1, which in turn favors end joining by blocking resection. In G1 phase when homologous template absent, ATM-53BP1 axis directs breaks toward classical non-homologous end joining pathway that directly ligates ends after minimal processing by Ku70/Ku80 heterodimer, DNA-PKcs, and XRCC4-DNA ligas
Ref: Marechal & Zou, Genes Dev 2013, DNA Damage Response; Scully et al., Cell 2019, DSB Repair Choice.
