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A powerful weapon to attack cancer: Why do scientists focus on APE1?
In today's medical research, cancer is one of the major threats to human health, and researchers have been looking for more effective treatments. Recently, APE1 (human AP-terminal nuclease 1) has become the focus of scientific research due to its key role in the DNA repair process. The way this enzyme operates and its function in cancer cells make it a potential therapeutic target, especially in the context of cancer chemotherapy.
APE1 plays an indispensable role in the DNA gene repair process, ensuring the integrity and stability of DNA.
Function and structure of APE1
APE1 is an enzyme involved in the DNA base excision repair (BER) pathway, which mainly processes damaged or mismatched nucleotides in DNA. During this process, APE1 creates a gap at the site of base loss, which also provides an entry point for subsequent repair reactions. APE1 belongs to the second class of AP-terminal nucleases and requires magnesium ions to enter the active site to exert its repair function.
APE1 contains several amino acid residues in its structure, which enable it to selectively react with AP sites and rapidly repair DNA damage.
Catalytic mechanism of APE1
APE1 creates a gap at the abond site through a simple acyl substitution mechanism. In the specific process, the Asp210 residue deprotonates a water molecule, anchors to the reactive site of DNA and attacks the nucleotide. As the electrons move, an oxygen atom is detached to form a free 5' phosphate group and produce a free 3'-OH end on a normal nucleotide, a process that also requires the stabilization of magnesium ions.
Inhibitors of APE1
Studies of APE1 have revealed several known inhibitors, such as 7-nitroindole-2-carboxylic acid (NCA) and locanone. The structures of these inhibitors are similar to the carbon ring of deoxyribose sugar, but lack the corresponding nucleotide group, and can hydrogen bond with the active site of APE1, thereby preventing the enzyme from catalyzing the reaction.
These findings provide new ideas for cancer treatment, as inhibition of AEP1 may increase the sensitivity of cancer cells to chemotherapy.
Anti-cancer potential of APE1
Due to the indispensable role of APE1 in DNA repair pathways, researchers hope to exploit the enzyme's function to develop new anti-cancer strategies. Inhibiting the activity of APE1 can lead to increased sensitivity of tumor cells to chemotherapy, thereby promoting cancer cell death. Especially when facing tumor cells that are resistant to traditional treatments, intervention of APE1 may become a breakthrough.
Characters of APE2
Compared to APE1, APE2 showed weaker AP-terminal nuclease activity, but performed well in other functions, such as its 3'-5' exonuclease activity. APE2 can efficiently hydrolyze different types of DNA structures and participate in the DNA damage response of ATR-Chk1 when faced with oxidative stress, showing its importance in cell repair.
In summary, APE1, as a potential tool for targeted cancer therapy, may have broader application prospects in future cancer research and treatment. In this context, we can't help but ask, will AAP1 become a new hope for cancer treatment?
