What is Base Excision Repair (BER)?
Base Excision Repair (BER) is a critical cellular mechanism that corrects
small base lesions in DNA. These lesions can arise due to oxidative stress, alkylation, deamination, or spontaneous hydrolysis. BER is vital for maintaining genomic integrity by rectifying these minor yet potentially mutagenic damages.
How Does BER Function?
The BER pathway involves several steps:
1.
Damage Recognition: Specific
DNA glycosylases recognize and remove the damaged base, creating an abasic site (AP site).
2.
AP Site Processing: An
AP endonuclease cleaves the DNA backbone at the AP site.
3.
DNA Synthesis:
DNA polymerase fills in the missing nucleotide.
4.
Ligation: The nick in the DNA strand is sealed by a
DNA ligase.
What Are the Implications of BER Deficiency?
Defects in the BER pathway can lead to an accumulation of DNA damage, increasing the risk of mutations and cancer. Genetic polymorphisms in BER-related genes have been linked to a heightened susceptibility to various cancers and other diseases. Additionally, BER-deficient cells are more sensitive to certain
chemotherapeutic agents, which can be exploited in cancer treatment strategies.
BER and Chemical Toxicity
Several chemicals, such as
alkylating agents and
polycyclic aromatic hydrocarbons (PAHs), can specifically target DNA bases, leading to lesions that are primarily repaired by BER. Understanding the interplay between chemical exposure and BER efficiency can provide insights into the mechanisms of toxicity and help in developing preventive and therapeutic interventions.
How Can BER Be Assessed?
BER activity can be assessed using various biochemical and molecular techniques.
DNA repair assays can quantify the efficiency of BER in cell extracts. Additionally, monitoring the expression levels of key BER enzymes through
qPCR or Western blotting can provide insights into the cellular response to DNA damage.
Future Directions in BER Research
Ongoing research aims to elucidate the detailed mechanisms of BER and its regulation under different physiological and pathological conditions. Understanding the impact of
environmental factors and genetic variability on BER can lead to better risk assessment and the development of novel therapeutic strategies for diseases associated with impaired DNA repair.
