DNA, or deoxyribonucleic acid, serves as the fundamental blueprint containing all the instructions necessary for the development, functioning, growth, and reproduction of every known living organism. Cells possess an inherent and continuous ability to correct damage to this important molecule. This natural process is often referred to as “wild type repair” or “wt repair,” representing the cell’s baseline, healthy repair capacity.
Understanding DNA Damage
The constant maintenance of DNA is a necessity because it faces a relentless assault from various sources, both internal and external. Within the cell, errors can occur during DNA replication, where the copying machinery might insert a “wrong letter” or base into the sequence, creating a mismatch. Metabolic byproducts, such as reactive oxygen species generated during normal cellular processes, can also chemically alter DNA bases or even break the DNA strands.
Beyond internal factors, environmental elements contribute significantly to DNA damage. Ultraviolet (UV) radiation from sunlight is a common external culprit, causing adjacent DNA bases to link abnormally, forming what are known as pyrimidine dimers. Ionizing radiation, found in medical imaging or natural background radiation, can lead to more severe damage, including double-strand breaks where both strands of the DNA helix are severed. Exposure to various chemicals, including those in tobacco smoke or industrial pollutants, can also modify DNA bases, while certain viruses can integrate their genetic material into the host’s DNA, disrupting its integrity.
How Cells Repair DNA
Cells employ a sophisticated array of mechanisms to detect and mend the constant stream of DNA damage, collectively referred to as “wild type repair.” One common strategy is excision repair, where damaged sections of DNA are removed and replaced with correct ones. This broad category includes several distinct pathways, each specialized for different types of lesions.
Base Excision Repair (BER)
Base excision repair (BER) focuses on repairing small, non-helix-distorting damage, such as chemically modified or incorrect bases. Specific enzymes called DNA glycosylases recognize and remove the damaged base, leaving a gap in the DNA strand. A different enzyme then cuts the sugar-phosphate backbone, and DNA polymerase fills the gap with the correct nucleotide, with DNA ligase sealing the final break. This pathway is particularly important for correcting damage from oxidation and deamination.
Nucleotide Excision Repair (NER)
For larger, bulky lesions that distort the DNA helix, such as those caused by UV radiation, nucleotide excision repair (NER) is activated. NER involves protein complexes that recognize the distortion, followed by dual incisions on either side of the damaged section by endonucleases. This creates a larger gap, which DNA polymerase then fills using the undamaged strand as a template, and DNA ligase completes the repair. NER is divided into global genome NER, which surveys the entire genome, and transcription-coupled NER, which specifically repairs damage on actively transcribed DNA strands.
Mismatch Repair (MMR)
Mismatch repair (MMR) is another important pathway, primarily correcting errors that occur during DNA replication, such as incorrectly paired bases that escaped the initial proofreading by DNA polymerase. This system identifies the mismatched base pair, removes a segment of the newly synthesized strand containing the error, and then resynthesizes the correct sequence.
Double-Strand Break Repair (HR & NHEJ)
For more severe damage, like double-strand breaks where both DNA strands are broken, cells have specialized pathways. Homologous recombination (HR) uses an undamaged homologous DNA molecule, often a sister chromatid, as a template to accurately repair the break. Alternatively, non-homologous end joining (NHEJ) directly ligates the broken ends, a process that is faster but can be more prone to errors if nucleotides are lost.
What Happens When DNA Repair Goes Wrong
When the natural DNA repair mechanisms, or “wild type repair,” are overwhelmed or fail to function correctly, the consequences for cellular health can be significant. Unrepaired or incorrectly repaired DNA lesions can lead to permanent changes in the genetic code, known as mutations. These mutations can alter the instructions for building proteins, potentially disrupting normal cellular processes.
The accumulation of such mutations is a major contributing factor to the development of various diseases, with cancer being a prominent example. Many cancers arise from an accumulation of DNA damage and errors in repair genes, which can lead to uncontrolled cell growth and division.
Beyond cancer, faulty DNA repair can also contribute to premature aging, as cells accumulate damage over time, affecting their ability to function optimally. Certain genetic disorders are also directly linked to inherited defects in specific DNA repair pathways.