The PP2A phosphatase counteracts the function of the 9-1-1 axis in checkpoint activation

• DOI: 10.1016/j.celrep.2023.113360
• Publication Date: 2023-10-29T15:32:59Z
• Authors: Erika Casari; Paolo Pizzul; Carlo Rinaldi; Marco Gnugnoli; Michela Clerici; Maria Pia Longhese
• Keywords: CHEK1; Checkpoint Kinase 2

DNA damage elicits a checkpoint response depending on the Mec1/ATR kinase, which detects presence of single-stranded and activates effector kinase Rad53/CHK2. In Saccharomyces cerevisiae, one signaling circuits leading to Rad53 activation involves evolutionarily conserved 9-1-1 complex, acts as platform for binding Dpb11 Rad9 (referred axis) generate protein complex that allows Mec1 activation. By examining effects both loss-of-function hypermorphic mutations, here, we show Cdc55 Tpd3 subunits PP2A phosphatase counteract axis. The lack this inhibitory function results in DNA-damage sensitivity, sustained checkpoint-mediated cell-cycle arrest, impaired resection double-strand breaks. This anti-checkpoint role depends capacity interact with Ddc1 Ddc1-Dpb11 formation by preventing recognition phosphorylated Thr602.