Schematic network of CDK- and ATM/ATR-mediated regulatory cycles of meiotic DSB timing and number in S. cerevisiae. (A) CDK phosphorylates Mer2 during pre-meiotic DNA replication [114,115,120]. (B) Phosphorylated Mer2 recruits Rec114, Mei4, Spo11 and other DSB proteins to DSB hotspot sites [45,120,121]. (C) DSB formation catalyzed by Spo11 and accessary proteins [4,66]. (D) Recurrent DSB formation activates TEL1/MEC1-dependent positive- and negative-feedback loops, which then restrains Spo11 activity and regulates the rate and number of DSB formation [136,140,147,156]. (E) Cis DSB interference mediated by TEL1 reduces the frequency of coincident DSB formation at the region adjacent to an already-formed DSB [143,149]. Trans inhibition mediated by TEL1 and MEC1 describes the ability of a DSB formation on one chromosome to suppress DSB formation on its homolog and sister chromatid at the same or adjacent regions [141].