Base Excision Repair (BER) is a critical cellular mechanism that repairs damaged DNA throughout the cell cycle. It is primarily responsible for correcting small, non-helix-distorting base lesions resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. This pathway is essential for maintaining the
integrity of the genome and preventing mutations that could lead to cancer.
The BER pathway involves several key steps and enzymes. Initially, a
DNA glycosylase recognizes and removes the damaged base, creating an abasic site (AP site). An AP endonuclease then cleaves the DNA backbone at this site. Subsequently, a DNA polymerase inserts the correct nucleotide, and finally, DNA ligase seals the nick to complete the repair.
BER and Cancer
Efficient BER is crucial for preventing
mutations that can lead to cancer. Defects in BER can result in the accumulation of DNA damage, which may cause genomic instability and promote carcinogenesis. For instance, mutations in the genes encoding DNA glycosylases or other BER proteins can lead to a higher predisposition to cancer.
BER in Cancer Therapy
Targeting BER mechanisms can enhance the efficacy of certain
chemotherapeutic agents. For example, inhibitors of BER enzymes can sensitize cancer cells to DNA-damaging agents, increasing their cytotoxicity. This strategy is being explored in combination therapies to improve treatment outcomes for cancer patients.
Clinical Implications
Understanding the role of BER in cancer can lead to the development of novel diagnostic and therapeutic approaches. For instance, assessing the status of BER pathways in tumors can help predict the response to specific treatments and guide personalized therapy. Moreover, targeting BER defects may provide new avenues for cancer prevention and treatment.
Future Directions
Ongoing research aims to elucidate the detailed mechanisms of BER and its interaction with other DNA repair pathways. Advances in this field could lead to the discovery of new biomarkers for early cancer detection and the development of more effective and less toxic therapeutic strategies.
