► Plk1 phosphorylates Rad51 recombinase at S14 in a highly specific manner ► Rad51 phosphorylation at S14 triggers subsequent phosphorylation at T13 by CK2 ► T13-phosphorylated Rad51 binds to the Nijmegen breakage syndrome gene product, Nbs1 ► Rad51 binding to Nbs1 is important for cellular resistance to genotoxic stresses. The gene discussed is RAD51; the disease is Down syndrome.