TLK1

TLK1, or Tousled-like kinase 1, is a serine/threonine protein kinase in humans that is a member of the Tousled-like kinase family. It is the mammalian homolog of the Drosophila Tousled gene and is primarily localized in the nucleus. TLK1 is active during S phase of the cell cycle and plays a role in DNA replication and chromatin assembly, contributing to genome stability by coordinating nucleosome formation as DNA is replicated and repaired.

In its function, TLK1 phosphorylates histone chaperones such as ASF1, which helps regulate histone deposition during chromatin maturation. Through these interactions with ASF1 and other chromatin assembly factors, TLK1 supports proper nucleosome assembly after DNA synthesis and repair. TLK1 activity is linked to the DNA damage response and is modulated by signaling pathways that respond to replication stress, helping to integrate chromatin regulation with genome maintenance.

Regulation of TLK1 involves cell cycle cues and DNA damage signaling. The activity of TLK1 can be influenced by checkpoint pathways that coordinate replication and repair processes, ensuring that chromatin assembly does not proceed unchecked during stress. TLK1 also has a close functional relationship with related kinases in the same family, particularly TLK2, which can have overlapping roles in chromatin dynamics.

Clinically and in research contexts, dysregulation of TLK1 has been observed in some cancers, and its function affects cellular sensitivity to DNA-damaging agents. As a result, TLK1 is investigated as a potential target for cancer therapy, with studies exploring inhibitors and genetic manipulation to modulate replication stress responses.