Spread the love

Definition: How can DNA repair mechanisms be affected by oxidative stress?

Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the ability of cells to detoxify them or repair the resulting damage. DNA repair mechanisms play a crucial role in maintaining the integrity of the genome and preventing the accumulation of mutations that can lead to various diseases, including cancer and aging.

Under normal physiological conditions, cells have evolved sophisticated DNA repair pathways to counteract DNA damage caused by endogenous and exogenous factors. However, oxidative stress can overwhelm these repair mechanisms and impair their efficiency, leading to the accumulation of DNA lesions.

One of the primary sources of oxidative stress is the production of ROS during normal cellular metabolism. ROS, such as superoxide anion (O2•−), hydrogen peroxide (H2O2), and hydroxyl radical (•OH), can directly damage DNA by causing base modifications, DNA strand breaks, and DNA-protein crosslinks. Additionally, ROS can indirectly induce DNA damage by oxidizing cellular components, such as lipids and proteins, which can generate secondary reactive species that can attack DNA.

See also What is the role of DNA in genetic mutations?

The impact of oxidative stress on DNA repair mechanisms is multifaceted. Firstly, ROS can directly damage proteins involved in DNA repair, impairing their function and stability. For example, ROS can oxidize and inactivate key enzymes involved in base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR), among others.

Secondly, oxidative stress can affect the availability and activity of DNA repair enzymes. ROS can oxidize and degrade the cofactors required for the proper functioning of repair enzymes, leading to their reduced activity. Furthermore, oxidative stress can modulate the expression of DNA repair genes, either by directly damaging the DNA sequences regulating their expression or by activating signaling pathways that alter their transcriptional regulation.

See also Why are sirtuins important for maintaining mitochondrial function?

Lastly, oxidative stress can interfere with the recognition and processing of DNA lesions by repair enzymes. ROS-induced DNA modifications can alter the structure and stability of DNA, making it more difficult for repair enzymes to recognize and repair the lesions. Moreover, ROS can induce DNA strand breaks that can overwhelm the repair capacity of the cell, leading to the persistence of unrepaired DNA damage.

In conclusion, oxidative stress can have profound effects on DNA repair mechanisms. By directly damaging repair proteins, affecting their availability and activity, and interfering with the recognition and processing of DNA lesions, oxidative stress can compromise the cell’s ability to maintain genomic integrity. Understanding the impact of oxidative stress on DNA repair is crucial for elucidating the mechanisms underlying aging and age-related diseases and developing strategies to mitigate their effects.

See also What is the role of social support in promoting longevity?

Keywords: repair, oxidative, stress, mechanisms, damage, enzymes, lesions, directly, leading