Bacteria have developed ligase to repair brakes in their DNA, so ligase occurs naturally in bacteria. Bacteria use $NAD^+$ as energy source, eucaryotes instead use ATP and have four different types of ligases
- DNA ligase I: connects Okazaki fragments of the lagging strand in DNA replication, and can also seal some repair and recombination fragments
- DNA ligase II: an alternatively spliced form of DNA ligase III that is only expressed in non-dividing cells.
- DNA ligase III: works with protein XRCC1, which is a DNA repair protein. DNA ligase III is a primary agent in sealing base excision-repairs and recombination fragments.
- DNA ligase IV: works with protein XRCC4, which is another DNA repair protein. DNA ligase IV is also important in sealing base excision-repairs and recombination fragments, especially during development
The following steps summarize an ligation mechanism:
- In the adenylation step, ATP binds ligase and cleaves away two inorganic phosphates
- The resulting AMP that binds ligase is transfered to 5' Phosephate of the DNA, which is thereby activated
- Displacement of the AMP from the phosphate leads to a covalent bond between the phosphate and the hydroxyl and a sealed DNA