ATM and ATR in the meiotic DSB response. (A) Mrg15 mutant germline clones (dashed circles) were identified by lack of GFP (see Materials and methods). Wild-type oocytes exhibit high levels of H2AV (500,000 fluorescence units), whereas Mrg15 mutant oocytes lack H2AV (132,000 fluorescence units, similar to background), demonstrating that Mrg15 is required for the incorporation of H2AV into germline chromatin. Bars, 10 µm. (B) A model for the role of ATM and ATR in the regulation of DSB formation and the repair response. Both ATM and ATR are essential for DSB repair (not depicted) and phosphorylate H2AV. Only ATM provides a negative feedback signal to limit the total number of DSBs (red line). The maintenance of γ-H2AV near DSB sites requires continuous ATM or ATR activity as a result of rapid repair-independent H2AV exchange. An Mrg15-containing complex such as Tip60 may be required to incorporate unphosphorylated H2AV into the nucleosomes. It is not clear whether this occurs by direct exchange of γ-H2AV with H2AV as previously described in embryos (Kusch et al., 2004) or via H2A. At stage 5, the attenuation of H2AV incorporation could result in its eventual absence from the nucleosomes.