Biochemistry & Physiology: Open Access
Open Access

DNA is constantly exposed to damage from a variety of sources, including environmental factors such as UV radiation, chemical agents, and physical stress, as well as endogenous factors like oxidative stress and replication errors. These damages, if left unrepaired, can lead to mutations, chromosomal instability, and ultimately, the development of diseases such as cancer. To maintain cellular integrity, organisms have evolved intricate and highly regulated DNA repair mechanisms that detect and repair DNA damage efficiently. Among the most crucial DNA repair pathways are base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR), and non-homologous end joining (NHEJ), each with distinct molecular mechanisms but ultimately serving the common purpose of maintaining genome integrity. The repair of DNA lesions is not merely a corrective process but is tightly integrated with other cellular processes, including cell cycle regulation, apoptosis, and DNA replication. Furthermore, an understanding of DNA repair mechanisms has significant implications for therapeutic strategies in the treatment of diseases related to genomic instability. DNA repair defects are often observed in cancer cells, where mutations in repair proteins lead to resistance to chemotherapy and radiotherapy [1]. Similarly, genetic disorders resulting from defective DNA repair mechanisms emphasize the critical nature of these pathways in human health. In recent years, there have been tremendous advancements in elucidating the molecular details of DNA repair processes, with new repair proteins and complex regulatory networks being discovered. These insights have not only enhanced our understanding of fundamental cellular processes but also paved the way for the development of targeted therapies aimed at modulating DNA repair pathways. The ongoing research in DNA repair is providing promising avenues for treating various cancers and genetic disorders, making this field a cornerstone of modern biomedical science.

Methods

This review was conducted by compiling and synthesizing recent scientific literature on DNA repair mechanisms, with a particular focus on primary repair pathways such as base excision repair, nucleotide excision repair, homologous recombination, and non-homologous end joining. Peer-reviewed journal articles, experimental studies, and reviews from the past two decades were analyzed to provide an updated overview of DNA repair processes. Databases such as PubMed, Google Scholar, and Scopus were searched using keywords such as “DNA repair,” “genomic instability,” and “DNA repair pathways.” We also examined the molecular components involved in each repair pathway, including key enzymes, repair proteins, and regulatory factors. Emphasis was placed on studies that explore the molecular mechanisms behind DNA damage detection, repair initiation, and the role of cellular signaling pathways in maintaining repair efficiency. Additionally, we reviewed the role of DNA repair in disease progression, particularly cancer, and its therapeutic implications [2].

Results

Recent studies have significantly enhanced our understanding of DNA repair mechanisms, revealing novel insights into the molecular components involved and the intricate regulation of these pathways. In base excision repair (BER), the identification of DNA glycosylases has clarified the initial step of removing damaged bases, followed by repair synthesis and ligation. Nucleotide excision repair (NER) has been shown to utilize a highly coordinated mechanism for detecting bulky DNA lesions caused by UV radiation [3]. Furthermore, homologous recombination (HR) and non-homologous end joining (NHEJ) have been found to play complementary roles in the repair of double-strand breaks, with HR operating during the S and G2 phases and NHEJ being predominant in the G1 phase. Additionally, recent research has identified several novel proteins, such as the RAD51 paralogs and the MRN complex, which are integral to the accurate repair of DNA damage. Several of these proteins act as scaffolding factors, bringing together other repair proteins at sites of damage. Importantly, a growing body of evidence suggests that DNA repair mechanisms are intimately linked to cell cycle regulation and apoptosis. Disruptions in repair pathways often lead to an accumulation of DNA damage, causing genomic instability and contributing to cancer development. Furthermore, cancers often exhibit altered DNA repair pathways that make them resistant to certain chemotherapeutic agents, highlighting the importance of understanding repair processes in the context of therapy resistance. Genetic disorders, such as Xeroderma Pigmentosum and Ataxia-Telangiectasia, continue to provide key insights into the role of DNA repair in maintaining cellular integrity, emphasizing the severe consequences of repair deficiencies [4].

Discussion

The advances in understanding DNA repair mechanisms have profound implications for both basic biology and clinical applications. Defects in DNA repair pathways contribute significantly to genomic instability, a hallmark of cancer cells. Cancer cells often harbor mutations in repair genes that allow them to survive and proliferate despite the accumulation of DNA damage [5]. This makes tumors more difficult to treat with conventional therapies such as chemotherapy and radiation, which typically rely on inducing DNA damage. As such, targeting DNA repair pathways, either by inhibiting repair in cancer cells or by enhancing repair in normal cells, has become an area of active research. For example, inhibitors of DNA repair proteins like PARP inhibitors have shown promise in treating cancers with defective repair pathways, such as BRCA1/2 mutant cancers. Furthermore, the interplay between DNA repair and cellular processes like the cell cycle and apoptosis is an essential area for investigation [6,7]. Understanding how cells decide to repair damage versus undergoing programmed cell death could open new avenues for therapeutic interventions. Additionally, the discovery of novel DNA repair proteins and their interactions with existing repair mechanisms has opened up new possibilities for developing targeted therapies that modulate these pathways. Research in DNA repair is also providing valuable insight into aging and the development of genetic disorders, where repair defects can lead to early onset diseases. The role of DNA repair in maintaining genome stability underscores its significance in cellular health and longevity [8-10].

Conclusion

DNA repair is a critical process for maintaining cellular integrity and preventing the accumulation of genetic mutations that could lead to disease. Over the years, significant advancements have been made in understanding the molecular mechanisms underlying DNA repair, particularly in key pathways such as base excision repair, nucleotide excision repair, homologous recombination, and non-homologous end joining. These findings have not only provided valuable insights into the basic biology of DNA repair but also laid the groundwork for therapeutic strategies aimed at modulating these pathways. The growing understanding of how DNA repair mechanisms interact with cellular processes, such as the cell cycle and apoptosis, continues to enhance our ability to develop targeted therapies for cancer and genetic disorders. The interplay between DNA repair and disease progression highlights the need for ongoing research in this field. As we continue to uncover the complexities of DNA repair, it holds promise for the development of novel treatments and interventions that could improve patient outcomes and address a range of diseases associated with genetic instability.

Acknowledgement

None

Conflict of Interest

None

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