TLK2, a member of the Ser/Thr protein kinase family, is rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. The TLK2 enzyme is cell-cycle regulated, with maximal activity in S-phase. It is inactivated by phosphorylation at Ser-750, potentially by CHK1. TLK2 heterodimerizes with TLK1. This nuclear protein is widely expressed, with presence in fetal placenta, liver, kidney, pancreas, heart and skeletal muscle tissues, and in several adult cell lines.