title: Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.
abstract: Two missense mutations occurring in different alleles of the DNA ligase I gene, encoding the major DNA ligase in proliferating mammalian cells, were detected in a human fibroblast strain (46BR). These cells exhibit retarded joining of Okazaki fragments during DNA replication and hypersensitivity to a variety of DNA-damaging agents. 46BR was derived from a patient who displayed symptoms of immunodeficiency, stunted growth, and sun sensitivity. A strongly reduced ability of DNA ligase I to form a labeled enzyme-adenylate intermediate correlated with the genetic defect in 46BR cells. The data indicate that human DNA ligase I is required for joining of Okazaki fragments during lagging-strand DNA synthesis and the completion of DNA excision repair.
authors.affiliation: Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, England.
authors.forename: D E
authors.initials: DE
authors.lastname: Barnes
authors.forename: A E
authors.initials: AE
authors.lastname: Tomkinson
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: T
authors.initials: T
authors.lastname: Lindahl
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001816:Bloom Syndrome / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment
chemical_list: C000607892:LIG1 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP