DNA LIGASES ( MOLECULAR GLUE) :

                            DNA  LIGASES 

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     DNA ligase is an enzyme that catalyzes the formation of phosphodiester bonds between the 3'-OH and 5'-phosphate ends of adjacent DNA strands, resulting in the formation of a covalent bond between the two strands.

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Classification:

DNA ligases are classified into different families based on their primary sequence, structure, and function.

The four major families of DNA ligases are:

• ATP-dependent DNA ligases: These ligases use ATP as a cofactor to catalyze the ligation reaction. They are found in bacteria, archaea, and eukaryotes.

• NAD-dependent DNA ligases: These ligases use NAD+ as a cofactor to catalyze the ligation reaction. They are found in bacteria and viruses.

• Adenylation domain-dependent DNA ligases: These ligases have an adenylation domain that activates the 5'-phosphate end of the DNA substrate, which is then ligated to the 3'-OH end of the other DNA substrate. They are found in bacteria and some viruses.

• XRCC1-like DNA ligases: These ligases are involved in the repair of DNA single-strand breaks (SSBs) and are found in eukaryotes.

                   DNA Ligase (molecular glue):

Mechanism of Action:

The catalytic cycle of DNA ligase involves three steps:

• Adenylation
• Transfer
• Ligation

• In the first step, the ligase binds ATP or NAD+ and adenylates the ligase active site lysine residue, forming an enzyme-AMP complex.
• In the second step, the activated 5'-phosphate end of the DNA substrate is covalently linked to the AMP molecule in the ligase active site, forming an enzyme-DNA-AMP intermediate.
• In the third step, the AMP molecule is transferred to the 3'-OH end of the other DNA substrate, forming a DNA-DNA intermediate, which is then sealed by the formation of a phosphodiester bond between the two strands.

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DNA is the building block of life and its maintenance is necessary for the proper functioning of living organisms. However, DNA damage is inevitable due to various internal and external factors such as exposure to radiation, reactive oxygen species, and other environmental agents. The ability of cells to repair DNA damage is essential to prevent mutations and ensure genomic stability. DNA ligase is a key enzyme involved in DNA repair, replication, and recombination.