DNA ligase I is dephosphorylated during the execution step of etoposide-induced apoptosis.

We have previously shown that the recruitment of hLigI to replication factories is mediated by a short sequence referred as RFTS (Replication Factory Targeting Sequence) that corresponds to an evolutionary conserved PCNA binding site. The interaction with PCNA affects also the phosphorylation status of Ser66 of hLigI during the cell cycle. More recently, we have observed that in HeLa cells etoposide-induced double strand breaks (DSBs) cause the relocalization of hLigI, PCNA and replication protein-A (RPA), leading to the dispersal of replication factories and to the formation of DNA repair foci. Reorganization of the subnuclear compartments was accompanied by a transient phosphorylation of the p32 subunit of RPA and by a transient dephosphorylation of Ser66 on hLigI. Taken together, these data indicate that during cell cycle and DNA repair the activity of hLigI is strictly regulated by phosphorylation/dephosphorylation.