Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.
Article Details
- CitationCopy to clipboard
Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T
Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.
Cell. 1992 May 1;69(3):495-503.
- PubMed ID
- 1581963 [ View in PubMed]
- 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.