Practice question

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 ligase IV complex. This pathway can operate throughout cell cycle but dominates in G1, preserving genome stability at cost of small deletions. Base excision repair handles oxidized bases via glycosylases like OGG1, nucleotide excision repair removes bulky UV adducts via XPA-XPC factors, mismatch repair corrects mispaired bases post-replication via MutS homologs, none directly activated by ATM for DSBs. Thus ATM orchestrates DSB response favoring NHEJ in G1 through histone modifications and mediator recruitment, while also signaling through CHK2-p53 to arrest cell cycle until repair completes or apoptosis initiated if damage excessive.