DNA repair

Definition

Target type: biologicalprocess

The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway. [PMID:11563486]

DNA repair is a fundamental cellular process that ensures the integrity of the genome by correcting damage to DNA molecules. DNA is constantly exposed to various damaging agents, both internal and external, such as reactive oxygen species, ultraviolet radiation, and chemical mutagens. These agents can cause a wide range of DNA lesions, including single-strand breaks, double-strand breaks, base modifications, and cross-links. If left unrepaired, these lesions can lead to mutations, genomic instability, and ultimately cell death or cancer. The process of DNA repair involves a complex interplay of different enzymes and proteins that work together to identify, remove, and repair damaged DNA segments. The specific mechanism of repair depends on the type of DNA damage. Here are some major DNA repair pathways:

* **Base Excision Repair (BER):** BER is responsible for repairing damaged or modified bases in DNA. It involves the removal of the damaged base by a DNA glycosylase, followed by endonuclease cleavage, gap filling by DNA polymerase, and ligation by DNA ligase. This pathway is particularly important for repairing damage caused by oxidative stress, alkylation, and deamination.
* **Nucleotide Excision Repair (NER):** NER is a more complex pathway that removes bulky DNA lesions, such as pyrimidine dimers induced by ultraviolet radiation. It involves the recognition of the lesion by a multiprotein complex, followed by unwinding of the DNA, excision of the damaged strand by an endonuclease, gap filling by DNA polymerase, and ligation by DNA ligase. NER is essential for protecting cells from the damaging effects of UV radiation and other environmental carcinogens.
* **Mismatch Repair (MMR):** MMR corrects mismatched bases that arise during DNA replication. It involves the recognition of the mismatch by a multiprotein complex, excision of the mismatched base by an exonuclease, gap filling by DNA polymerase, and ligation by DNA ligase. MMR is crucial for maintaining the fidelity of DNA replication and preventing mutations that can lead to cancer.
* **Double-Strand Break Repair (DSBR):** DSBR is a critical pathway for repairing double-strand breaks, which are the most severe type of DNA damage. There are two main DSBR pathways:
* **Homologous Recombination (HR):** HR uses a homologous DNA sequence as a template to repair the break. It involves the resection of the break ends, strand invasion of the homologous template, DNA synthesis, and ligation. HR is an error-free mechanism that maintains the integrity of the genome.
* **Non-homologous End Joining (NHEJ):** NHEJ directly joins the broken ends of DNA without the need for a homologous template. It involves the recognition of the break ends by a protein complex, processing of the ends, and ligation by DNA ligase. NHEJ is a more error-prone mechanism than HR but is essential for repairing breaks that occur outside of S phase when homologous templates are not available.

DNA repair is essential for maintaining genome stability and protecting cells from the damaging effects of environmental insults. Defects in DNA repair pathways can lead to an increased risk of cancer, premature aging, and other diseases. The complexity and redundancy of these pathways highlight the importance of DNA repair for maintaining cellular homeostasis and ensuring the faithful transmission of genetic information.'
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Proteins (65)

Compounds (809)