Phosphorylated PTEN participates in chromatin remodeling during the DNA damage response

The phosphatase PTEN is an important molecule for maintaining chromosome stability. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to the accumulation of structural and numerical chromosome instability. PTEN has many posttranslational modifications, including phosphorylation, acetylation and methylation; its modification level directly regulates protein levels and functions, thereby affecting the stability of the genome. It has been reported that Plk1, a Ser/Thr kinase, can directly phosphorylate PTEN at S380, impair its interaction with cdh1 and stabilize its association with chromatin. As the phosphorylation of PTEN at the STT motif is associated with the DNA damage response and Plk1 activity is inhibited when DNA damage occurs, it is not clear whether there are other upstream molecules that can regulate S380 phosphorylation, and if so, by what mechanism. We found that the ATM/Chk2 signaling pathway can affect PTEN p-S380 when DNA damage occurs and that PTEN p-S380, which may be regulated by ATM/Chk2, is involved in chromatin decondensation. These results suggest a role for PTEN modification by other kinases and provide a target for improving radiotherapy efficacy.