The discovery of DNA ligase by the Gellert, Lehman, Richardson, and Hurwitz teams in 1967 was a breakthrough in molecular biology. These essential enzymes maintain genome integrity and play a vital role in DNA replication and repair across all living organisms. By forming phosphodiester bonds, it ensures the seamless connection of Okazaki fragments on the lagging strand during replication.
DNA ligase require an energy molecule to facilitate these bonds, ensuring proper DNA synthesis and repair. Their significance extends beyond cellular functions, finding applications in molecular cloning, genetic diagnostics, cancer therapeutics, and next-generation sequencing technologies. Research indicates that most organisms have multiple ligases dedicated to distinct DNA repair pathways, including nucleotide excision repair, base excision repair, and nonhomologous end joining for double strand break repair.
With increasing demand for DNA replication enzymes -based diagnostics, a rising prevalence of genetic disorders, and growing research funding, the global ligase market is poised for substantial expansion. According to BIS Research, the global ligase market is projected to reach $651.4 million by 2032, up from $371.2 million in 2021, growing at a CAGR of 5.29%.
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DNA ligases are indispensable in DNA replication, ensuring genetic continuity. The process begins with helicase and gyrase unwinding the DNA. As DNA polymerase extends the leading strand, Okazaki fragments form on the lagging strand. However, gaps remain after RNA primer removal. At this stage, DNA ligase bridges these gaps, securing a continuous, stable DNA strand through phosphodiester bond formation.
Since DNA ligation is essential for DNA replication and repair, DNA ligases have emerged as a promising target for cancer treatment. Its inhibitors block ligase activity, preventing cancer cells from repairing DNA damage, thereby enhancing the effectiveness of genotoxic drugs.
Despite challenges posed by multiple DNA ligases with overlapping functions in human cells, structure-based drug discovery has identified promising inhibitors. For instance, L67, a DNA ligase inhibitor, demonstrated high efficacy in combination with PARP inhibitors in leukemia patient samples and cancer cell lines. By targeting DNA repair deficiencies, these inhibitors present new opportunities for precision oncology.
DNA ligases are fundamental to genomic stability and are driving advancements in biotechnology, genetics, and cancer therapeutics. Their role in DNA replication, repair, and targeted therapies highlights their growing importance in medical research and molecular diagnostics. As new innovations emerge, the global ligase market will shape the future of genomics, precision medicine, and therapeutic drug development.
