FIG. 8.

Functional interaction of ATM and the Mre11 complex. The Mre11 complex relocalization in response to DNA damage (37) and during DNA replication is independent of ATM. We therefore infer that the Mre11 complex is situated at spontaneously arising DNA breaks or proximal to sites of DNA replication as part of its function in normally growing cells. We propose that upon the induction of DNA damage, ATM is activated and acts on the Mre11 complex engaged at those structures. This implies that the complex's role in S-phase checkpoint activation is partially dependent upon ATM effects on the complex's function at those sites. It is conceivable that ATM modification may also enhance Mre11 complex DNA repair functions, as has been suggested for Tel1-dependent modification of the S. cerevisiae Mre11 complex (65).