Cell cycle checkpoints, such as the S-phase checkpoint, delay cell division to give the cell time to repair any damaged DNA. Here it is shown that the MLL gene — frequently disrupted in leukaemia — is part of the S-phase checkpoint. When DNA is damaged, MLL is phosphorylated by the ATR protein, causing MLL to accumulate on chromatin and methylate histone H3 on lysine 4. This delays DNA replication. MLL translocations, such as those that occur in leukaemia, disrupt this pathway and cause genomic instability.
- Han Liu
- Shugaku Takeda
- James J.-D. Hsieh
