Which checkpoint pathway primarily responds to double-strand breaks in DNA?

• A. ATM-Chk2
• B. ATR-Chk1
• C. p53-Chk2 axis
• D. BRCA1-Chk1 axis

Answer: (A)

When double-strand breaks occur, the cell first relies on the ATM kinase pathway. The break is sensed by the MRN complex, which activates ATM. Active ATM then phosphorylates downstream effectors, especially Chk2 and p53. This ATM-Chk2 axis enforces cell cycle arrest and initiates the repair process, giving the cell time to fix the break. ATR, by contrast, is primarily activated by replication problems and single-stranded DNA, not the clean double-strand break signal. The BRCA1-Chk1 axis participates in repair coordination during replication but is not the main checkpoint responding directly to a DSB. So the primary response to double-strand breaks is the ATM-Chk2 pathway.