Eukaryotic DNA ligases: structural and functional insights.
DNA ligases are required for DNA replication, repair, and recombination. In eukaryotes, there are three families of ATP-dependent DNA ligases. Members of the DNA ligase I and IV families are found in all eukaryotes, whereas DNA ligase III family members are restricted to vertebrates. These enzymes share a common catalytic region comprising a DNA-binding domain, a nucleotidyltransferase (NTase) domain, and an oligonucleotide/oligosaccharide binding (OB)-fold domain. The catalytic region encircles nicked DNA with each of the domains contacting the DNA duplex. The unique segments adjacent to the catalytic region of eukaryotic DNA ligases are involved in specific protein-protein interactions with a growing number of DNA replication and repair proteins. These interactions determine the specific cellular functions of the DNA ligase isozymes. In mammals, defects in DNA ligation have been linked with an increased incidence of cancer and neurodegeneration.
Ellenberger
Tom
T
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. tome@biochem.wustl.edu
Tomkinson
Alan E
AE
D000818:Animals; D002384:Catalysis; D020134:Catalytic Domain; D004247:DNA / Q000737:chemistry; D011088:DNA Ligases / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D016678:Genome; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry
D010455:Peptides; D004247:DNA; D011088:DNA Ligases