What is DNA Repair?
DNA repair is a critical process in maintaining the integrity of the genome. It involves various mechanisms that detect and correct damage to the
DNA structures. These mechanisms ensure proper cellular function and prevent mutations that could lead to diseases such as cancer.
Main Types of DNA Damage
DNA can be damaged by various factors such as UV radiation, chemical agents, and oxidative stress. The main types of DNA damage include:
DNA Repair Mechanisms
There are several DNA repair mechanisms that cells employ to fix damaged DNA. These include: Base Excision Repair (BER)
BER is primarily responsible for repairing small lesions such as
oxidative base damage and
single-strand breaks. The process involves the removal of the damaged base by a DNA glycosylase, followed by cleavage of the resulting abasic site by an AP endonuclease. The gap is then filled by DNA polymerase and sealed by DNA ligase.
Nucleotide Excision Repair (NER)
NER is crucial for removing bulky lesions, such as
thymine dimers caused by UV light. The NER pathway involves the recognition of the damage, excision of a short single-stranded DNA segment containing the lesion, and resynthesis of the removed DNA by DNA polymerase. The final step is sealing the nick by DNA ligase.
Mismatch Repair (MMR)
MMR corrects errors that escape proofreading during DNA replication, such as
base mismatches and small insertion-deletion loops. The MMR system recognizes the mismatched bases, excises the incorrect segment, and fills the gap with the correct sequence using the undamaged strand as a template.
Homologous Recombination (HR)
HR is a high-fidelity repair process for
double-strand breaks. It uses a homologous sequence as a template for accurate repair. This process is especially active during the S and G2 phases of the cell cycle when a sister chromatid is available as a template.
Non-Homologous End Joining (NHEJ)
NHEJ is an alternative pathway for repairing double-strand breaks, particularly in the absence of a homologous template. It involves the direct ligation of the broken ends, which can lead to the introduction of small insertions or deletions, making it a more error-prone mechanism compared to HR. Clinical Relevance of DNA Repair Mechanisms
Abnormalities in DNA repair mechanisms are linked to various
diseases, including cancer. For example, mutations in genes involved in NER can lead to
xeroderma pigmentosum, a condition that dramatically increases the risk of skin cancer. Understanding these mechanisms can aid in the development of
therapeutic strategies targeting defective DNA repair pathways in cancer treatment.
Conclusion
DNA repair mechanisms are essential for maintaining genomic stability and preventing disease. In histology, the study of these processes at the tissue level provides insights into cellular health and the development of pathological conditions. Continued research in this area holds promise for advancing medical science and improving therapeutic interventions.
