A BIN2-SOG1 molecular module regulates replication stress response independently on ATR

DNA replication stress poses a severe threat to genome stability. It is well-known that SOG1 plays a crucial role in DNA replication stress response in plants. Although ATM-mediated phosphorylation and CRL4 PRL1 -mediated polyubiquitination of SOG1 play important roles in regulating DNA damage response (DDR), the posttranslational modifications of SOG1 during the replication stress response are little known. Here we show that, during replication stress, the activity of the GSK3-like kinase BIN2 is activated by an unknown mechanism independent of ATR. Subsequently, BIN2 phosphorylates SOG1 at T244 and T249, which enhances SOG1 stability and transcriptional activity to activate DDR. Thus, our study demonstrated a pathway by which plants dynamically regulate replication stress response by a BIN2-SOG1 module.