Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks

• We review the roles of the evolutionarily conserved checkpoint kinases ATM/Tel1 and ATR/Mec1 in the response to DNA double-strand breaks (DSBs).
• We give a summary of the current literature on DSB processing.
• We discuss how ATM/Tel1 and ATR/Mec1 are activated by DNA double-strand breaks.
• We discuss the interplays between ATM/Tel1 and ATR/Mec1 signaling activities at DNA ends.

DNA double-strand breaks (DSBs) are highly hazardous for genome integrity because they have the potential to cause mutations, chromosomal rearrangements and genomic instability. The cellular response to DSBs is orchestrated by signal transduction pathways, known as DNA damage checkpoints, which are conserved from yeasts to humans. These pathways can sense DNA damage and transduce this information to specific cellular targets, which in turn regulate cell cycle transitions and DNA repair. The mammalian protein kinases ATM and ATR, as well as their budding yeast corresponding orthologs Tel1 and Mec1, act as master regulators of the checkpoint response to DSBs. Here, we review the early steps of DSB processing and the role of DNA-end structures in activating ATM/Tel1 and ATR/Mec1 in an orderly and reciprocal manner.