Experts state that our DNA, which carries genetic information, can be damaged due to various reasons, and among the most common causes of this damage are radiation (UV, X, and gamma rays), chemicals (cigarette smoke, toxins), viral infections, and naturally occurring metabolic processes in the body.
Molecular Biologist Res. Assist. Ayşegül Yanık noted that structural deteriorations in DNA can harm genetic information and threaten cell health, saying, “Methods that directly correct mutations in DNA are performed through gene therapy or genetic engineering methods involving gene editing technologies. CRISPR-Cas9 is one of the most powerful gene-editing tools developed in recent years. With this technology, a specific gene can be targeted, cut out, a healthy gene can be added, or the gene’s function can be modified.”
Üsküdar University, Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Res. Assist. Ayşegül Yanık shared important information about DNA damage, repair, and treatment methods at the genetic level within the scope of April 25 World DNA Day.
Our DNA Can Be Damaged by Environmental Factors
Res. Assist. Ayşegül Yanık noted that DNA is one of the most important molecules in our body, carrying genetic information, but added, “However, it is not always stable. It can be damaged due to environmental reasons and natural events occurring in our body or cells. Factors that damage DNA include radiation (UV, X-rays, gamma rays), cigarette smoke, toxic chemicals, environmental toxins, air pollution, and viral infections. These factors can lead to breaks in the DNA structure and cause changes in the base structures that form genetic information. Furthermore, some viruses can bind to our DNA and disrupt our genetic structure. This situation can lead to uncontrolled cell proliferation. Some substances formed as a result of metabolic events in our body, and errors that can occur during DNA self-replication, can also disrupt the structure of DNA. These errors are mostly repaired by our body.”
How Do Naturally Occurring DNA Repair Mechanisms Work in Our Cells?
Yanık stated that cells are programmed to ensure that genetic information is stored, protected, and transmitted from generation to generation correctly, adding, “For this reason, our cells have highly developed repair mechanisms that can recognize and correct damage in DNA. This is a spontaneously existing natural process. In this way, genetic information is protected, and cells continue their lives in a healthy manner. The cell recognizes structural defects on the DNA with special proteins. The damaged part of the DNA is cut out by special enzymes. A new piece is synthesized using the intact DNA template for the empty region, and the synthesized piece is then joined to the old DNA by enzymes present in the cell, ensuring the completion of the chain.”
What Problems Does Unrepaired DNA Lead To?
Yanık also stated that if damage occurring in DNA is not properly repaired, permanent mutations occur in cells, adding, “These mutations can occur anywhere in the DNA, as well as in genes responsible for cell growth, proliferation, and control of cell death. If this situation leads to uncontrolled cell proliferation, the risk of cancer increases. For example, when genes like BRCA1 and BRCA2 are disrupted, the risk of breast and ovarian cancer increases. If DNA repair is insufficient, nerve cell dysfunction and cell death can develop. This can lead to neurological diseases. DNA repair is also important during the development of immune cells. Disorders can lead to immunodeficiencies. Furthermore, DNA damage accumulates in cells over time. This slows down tissue regeneration, thus increasing the signs of aging.”
Intervention in DNA with CRISPR Technology…
Res. Assist. Ayşegül Yanık, stating that the concept of DNA repair or improvement means correcting errors in DNA or genetic mutations, continued:
“It aims to support natural repair processes or treat diseases by making direct genetic corrections. DNA repair or improvement occurs with drugs that activate DNA repair enzymes or with direct genetic interventions. Methods that directly correct mutations in DNA are performed through gene therapy or genetic engineering methods involving gene editing technologies (e.g., cutting out a faulty gene with CRISPR and inserting a healthy one). CRISPR-Cas9 is one of the most powerful gene-editing tools developed in recent years. With this technology, a specific gene can be targeted, cut out, a healthy gene can be added, or the gene’s function can be modified.”
Which Diseases Does It Offer Hope For?
Yanık stated that DNA improvement approaches are very important especially for genetic-based diseases because they can directly intervene in problems at the genetic level, adding, “Treatment approaches for DNA repair offer hope with CRISPR and gene therapy for genetic diseases such as sickle cell anemia, cystic fibrosis, Duchenne muscular dystrophy; rare genetic diseases like Spinal Muscular Atrophy (SMA); age-related diseases like Alzheimer’s; immune system diseases like SCID (Severe Combined Immunodeficiency), and some cancer diseases.”
What Stage Are Drugs and Gene Therapies In?
Res. Assist. Ayşegül Yanık also stated that some drugs targeting DNA repair mechanisms are currently in clinical use, adding, “While some are in the trial phase. Some drugs (e.g., PARP inhibitors) are already used in cancer treatment; these treatments aim to selectively kill cells with impaired DNA repair. Gene therapies, on the other hand, have passed clinical trials for some rare diseases, while trials for more common diseases are ongoing. Some FDA-approved gene therapies are available for spinal muscular atrophy and some eye diseases. Some CRISPR-based therapies are currently in early clinical trial stages. Sickle cell anemia treatment has been successfully applied and received FDA approval in 2024.”