Apoptosis is the programmed cell death used to maintain homeostasis and caused by stressors such as DNA damage. Apoptosis is the mechanism by which organisms can get rid of damaged, old, or useless cells without causing inflammation. Once the signal for apoptosis is received, the cell changes in a number of ways: The cell shrinks, the chromatins condense, the nucleus fragments, and the plasma membrane bubbles, also called "blebbing". Once this has happened, the cell is either consumed by surrounding cells or a macrophage.
DNA damage response (DDR) is the mechanism that takes over cells once DNA is damaged. It repairs DNA, stops cell division, or causes the cell to die, called apoptosis. The protein kinases that help regulate DDR are called ATM and ATR. ATR-dependent DDR can cause apoptosis. hMSH2 is also an important piece in activating the protein kinase ATR, and when hMSH2 isn’t there, cells with damaged DNA don’t go through apoptosis.
So far it has been thought that there were two essential proteins that mediate apoptosis. p53 causes apoptosis and Bcl-2 inhibits it. However, cells with the p53 protein removed that were subjected to DNA damage still underwent apoptosis. This means there must be some other mechanism that causes apoptosis due to DNA damage other than p53. Cells with damaged DNA, without p53, and with Bcl-2 did not undergo apoptosis (Bcl-2 inhibited it), but did stop dividing (most of them were stuck in the G1 or G2 phase). This suggests that there is a DNA damage G1 checkpoint in the cell cycle independent of p53. This means that for future cancer treatment, survival genes like the BCL2 gene must be dealt with as well as what to do when there is no p53.
The Bcl-2 family of proteins, which are located directly ahead of the damaged cells, serve as a gateway in the process of apoptosis. BAX/BAK makes up the gateway on the mitochondrial surface which leads to the intrinsic pathway. Antiapoptotic Bcl-2 and Bcl-XL bring the process to a halt. Apoptosis signaling pathways are being studied in an attempt to develop therapy for irregular apoptosis. Too much apoptosis can cause problems like Chronic Wasting Disease, while not enough apoptosis causes cancer. An example of this type of study is a study involving the pro-apoptotic protein Prostate Apoptosis Response Protein-4 or Par-4 that can be activated in colon cancer cells. It has been demonstrated that Par-4 can be increased in colon cancer cells by inhibiting Src.
At the Georgia Institute of Technology in the Laser Dynamics Laboratory, researchers were able to conjugate nanoparticles of gold and move them inside the nucleus of cancer cells using peptides. The research team took microscopic images and found that double-strand breaks in the DNA where the gold nanoparticles had been injected into the cancer cells’ nuclei. This nuclear targeting induces cytokinesis arrest, and binuclear formation of cells occurs after mitosis in this case. It was indicated that when the cells failed to separate and complete cell division, apoptosis occurred in those specific cells. When the experiment had reached 360 minutes, 35% of the population was stopped at the G1 phase and the rest of the cell population had slowed down at the M phase. Only a small percentage was able to break through and complete mitosis. The cells that had not been injected with gold nanoparticles were all able to complete mitosis.