Question

You are working for a large pharmaceutical company that is trying to develop new therapies to stop an aggressive form of breast cancer. Your goal is to develop several different therapies that seek to influence the abnormal control of cell cycle and apoptosis in these cancerous cells. You’ve worked out a mechanism to deliver your small molecules directly to the tumor, so that it is only taken up by specific cells (cancerous cells), however you are still working on your intracellular targets for this therapeutic strategy.

1)Recognition of persistent or highly abundant DNA double strand breaks can result in the induction of apoptosis. Explain how this might occur, including the relevant effectors that are activated in response to DNA double strand breaks and those that execute apoptosis. A complete answer will fully explain how apoptosis is induced and executed in this scenario.

Answer 1

Solution: DNA damages occurs to cell differently among these the most daunting is the double stranded breaks. The main recognizing factors during these break for atiin is through a pair of protein kinases called ATM and ATR. These kinases are recruited to sites of DNA damage. They then activates two other protein kinases namely Chk1 and Chk2. The Chk1 and Chk2 kinases initially activates downstream proteins to repair these errors. If the error seems to be irreperable then these kinase activates one key protein p53, which is a tumor supproser protein. The p53 then activates the pro-apoptotic proteins like bim/puma/noxa. Activated pro-apoptotic proteins induce intrinsic pathway of apoptosis and leads to the cell death. The pro-apoptotic proteins activate the apoptosis by inhibiting the anti-apoptotic priteins Bcl2 and Bclxl. This pave the way for oligomerization followed by pore formation on the mitochodrial membrane by Bak or Bax proteins. Through this pore Cytochrome C expells out of the mitochondria and in cytosol they combines with Apaf 1 protein to form apoptosome complex this then activates various caspases and ultimately lead to apoptosis.