Specialised large regions of inactive DNA and protein complexes may provide a sophisticated mechanism for defective cells to survive, reports a paper published online this week in Nature Cell Biology. These findings could have potential implications in cancer.
DNA damage triggers cells to die, or to stop dividing but remain alive in a dormant state known as cellular senescence. Senescent cells are marked by large-scale inactive DNA and protein complexes, known as Senescence-associated heterochromatic foci (SAHF), the function of which has remained unclear.
Fabrizio d’Adda di Fagagna and colleagues find that SAHF controls the level of the cell’s response to DNA damage. The presence of SAHF dampens the response to damaged DNA to sublethal levels, permitting cells to stop dividing and become senescent rather than die. The implication is that such cells could acquire additional changes over time, allowing them to bypass the proliferative arrest of senescence and to resume cell division, leading to cancer.
In accordance with this idea, SAHF is found in human cancers and a compound that removes SAHF from cancer cells also potentiates the DNA damage response and increases cell death. The researchers propose that these findings may prove important for cancer research, as they could be therapeutically exploited.