Fig. 7. Working model.

In normal cells undergoing DNA damage, CK2α regulates heterochromatin relaxation by phosphorylating HP1α, which promotes its dynamic dissociation with H3K9me3 and relocalization at DNA double-strand break sites (DSB), which facilitates DNA damage response and repair. Reducing CK2 activity leads to the accumulation of DNA damage, which leads to cellular senescence. Since CK2 activity is low in Zmpste24-deficient cells (progeria cells), CK2 inhibition by TBB aggravates extant DDR defects in senescent cells and results in apoptosis. CK2 activity determines the fate of cells undergoing varying degrees of DNA damage.