The Tousled-like kinases (TLKs) function in processes of chromatin assembly, 
including replication, transcription, repair, and chromosome segregation. TLKs 
interact specifically (and phosphorylate) with the chromatin assembly factor 
Asf1, a histone H3-H4 chaperone, histone H3 itself at Ser10, and also Rad9, a 
key protein involved in DNA repair and cell cycle signaling following DNA 
damage. These interactions are believed to be responsible for the action of TLKs 
in double-stranded break repair and radioprotection and also in the propagation 
of the DNA damage response. Hence, I propose that TLKs play key roles in 
maintenance of genome integrity in many organisms of both kingdoms. In this 
paper, I highlight key issues of the known roles of these proteins, particularly 
in the context of DNA repair (IR and UV), their possible relevance to genome 
integrity and cancer development, and as possible targets for intervention in 
cancer management.