<p>DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. A special enzyme, <a href="https://en.wikipedia.org/wiki/DNA_ligase" class="extiw" title="en:DNA ligase">DNA ligase</a> (shown here in color), encircles the double helix to repair a broken strand of DNA. DNA ligase is responsible for repairing the millions of DNA breaks generated during the normal course of a cell's life. Without molecules that can mend such breaks, cells can malfunction, die, or become cancerous. DNA ligases catalyse the crucial step of joining breaks in duplex DNA during <a href="https://en.wikipedia.org/wiki/DNA_repair" class="extiw" title="en:DNA repair">DNA repair</a>, <a href="https://en.wikipedia.org/wiki/DNA_replication" class="extiw" title="en:DNA replication">replication</a> and <a href="https://en.wikipedia.org/wiki/DNA_recombination" class="extiw" title="en:DNA recombination">recombination</a>, and require either Adenosine triphosphate (ATP) or Nicotinamide adenine dinucleotide (NAD+) as a cofactor. 
</p><p>Shown here is DNA ligase I repairing chromosomal damage. The three visable protein structures are: 
</p>
<ol><li>The DNA binding domain (DBD) which is bound to the DNA minor groove both upstream and downstream of the damaged area.</li>
<li>The OB-fold domain (OBD) unwinds the DNA slightly over a span of six base pairs and is generally involved in nucleic acid binding.</li>
<li>The Adenylation domain (AdD) contains enzymatically active residues that join the broken nucleotides together by catalyzing the formation of a phosphodiester bond between a phosphate and hydroxyl group.</li></ol>
It is likely that all mammalian DNA ligases (Ligases I, III, and IV) have a similar ring-shaped architecture and are able to recognize DNA in a similar manner. (See:<a rel="nofollow" class="external text" href="http://www.fhcrc.org/science/labs/stoddard/MCB_542/pascal_etal_2004_ligaseI.pdf">Nature Article 2004, <b>PDF</b></a>)
Tom Ellenberger, Washington University School of Medicine in St. Louis.
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