TLK2

TLK2 is the second tousled-like kinase in humans and shares with TLK1 the S phase-restricted activation and the phosphorylation of the histone chaperone ASF1 that couples DNA synthesis with nucleosome deposition. Genetic depletion of TLK2 compromises genome stability and cell proliferation, and the kinase shows synthetic lethal relationships with DNA repair defects. Amplification of the TLK2 locus with corresponding overexpression occurs in a subset of breast cancers, and the kinase has emerged as a candidate vulnerability in genomically unstable tumors. TLK2 mutations are also observed in neurodevelopmental disorder cohorts.