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2006, 21 November
Rendered image, software generated
Creative Commons - Wikipedia
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, DNA ligase (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 DNA repair, replication and recombination, and require either Adenosine triphosphate (ATP) or Nicotinamide adenine dinucleotide (NAD+) as a cofactor.
Shown here is DNA ligase I repairing chromosomal damage. The three visable protein structures are:
- The DNA binding domain (DBD) which is bound to the DNA minor groove both upstream and downstream of the damaged area.
- The OB-fold domain (OBD) unwinds the DNA slightly over a span of six base pairs and is generally involved in nucleic acid binding.
- 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.
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:Nature Article 2004, PDF)
Courtesy of Tom Ellenberger, Washington University School of Medicine in St. Louis.