Phosphoregulation of the checkpoint kinase Mec1.

Yeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. Mec1, in complex with Ddc2, is a 'sensor' of single stranded DNA, and phosphorylates numerous cell cycle and DNA repair factors to enforce cell cycle arrest and facilitate repair. Over the last several years, new techniques - particularly in structural biology - have provided molecular mechanisms for Mec1 function. It is becoming increasingly clear how post-translational modification of Mec1 and its interaction partners modulates the DNA damage checkpoint. In this review, we summarise the most recent work unravelling Mec1 function in the DNA damage checkpoint and provide a molecular context for its regulation by phosphorylation.