Changing of the guard: how ATM hands off DNA double-strand break signaling to ATR

Abstract

In a recent issue of Molecular Cell, Shiotani and Zou (2009) elucidate the biochemical mechanism underlying sequential ATM and ATR activation at DNA double-strand breaks, demonstrating that resection transforms ATM substrates into ATR substrates.

Figure 1. Blunt Double-Strand Breaks Are Recognized by MRN and ATM and Activate the ATM Kinase

In an ATM-dependent manner, MRN initiates 5′-end resection; resection is continued by other helicases and nucleases. The resected end is thereby transformed from a structure that activates ATM into a structure that activates ATR. Cell-cycle regulation of this transformation controls when ATR is activated and when breaks are repaired by homologous recombination.