February 17, 2023
DNA damage and repair
DNA is the genetic material that carries the blueprint for all living organisms. It is susceptible to damage from various internal and external factors, such as radiation, chemicals, and errors during replication. Fortunately, cells have evolved a complex and intricate system of DNA damage and repair mechanisms to maintain genomic stability and prevent diseases such as cancer.

DNA damage can take various forms, such as breaks in the DNA strands, chemical modifications of nucleotide bases, or cross-linking of DNA strands. Depending on the type and extent of damage, different repair mechanisms are activated. The primary DNA repair mechanisms include base excision repair, nucleotide excision repair, and double-strand break repair.

Base excision repair (BER) is the most common repair mechanism that targets damaged nucleotide bases. It involves the removal of the damaged base by a specific enzyme called a glycosylase, followed by cleavage of the sugar-phosphate backbone by an endonuclease. The gap is then filled by a DNA polymerase and sealed by a ligase enzyme. BER is particularly efficient in repairing oxidative damage caused by reactive oxygen species generated during normal cellular metabolism.

Nucleotide excision repair (NER) is another mechanism that targets a broad range of DNA damage, including bulky chemical adducts and UV-induced photoproducts. NER involves the recognition of the damaged DNA region by a complex of proteins, which then cleave the DNA on either side of the lesion. The gap is filled by a DNA polymerase and sealed by a ligase enzyme.

Double-strand break repair (DSBR) is the most complex repair mechanism that deals with the most severe form of DNA damage. DSBR can occur spontaneously or be induced by ionizing radiation or chemicals. It involves the recognition of the break by a complex of proteins, which then recruit other proteins to synapse the broken ends. The broken ends are then processed to generate compatible ends, which are then joined by a DNA ligase. DSBR can occur by two pathways: non-homologous end-joining and homologous recombination.

Non-homologous end-joining (NHEJ) is the simpler and more error-prone pathway that directly ligates the broken ends without the need for sequence homology. NHEJ can introduce small insertions or deletions at the junction site, which can potentially affect gene function or regulation.
Homologous recombination (HR) is the more complex and accurate pathway that relies on a homologous template to repair the broken ends. HR is activated when the cell is in the S or G2 phase of the cell cycle, where a sister chromatid is available as a template. HR involves the generation of a single-stranded DNA by the action of nucleases, which invades the homologous template and primes DNA synthesis. The newly synthesized DNA strand is then ligated with the original broken end to complete the repair process.

In conclusion, DNA damage and repair are fundamental processes that maintain the integrity of the genetic material and prevent genomic instability and disease. The complexity and diversity of DNA damage necessitate the activation of multiple repair mechanisms, each with its specific substrate and efficiency. Defects in DNA repair mechanisms can result in various genetic disorders and predisposition to cancer. Therefore, understanding the mechanisms of DNA damage and repair is crucial for both basic research and clinical applications.

This site was made on Tilda — a website builder that helps to create a website without any code
Create a website