Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents

DE Barnes, AE Tomkinson, AR Lehmann… - Cell, 1992 - cell.com
DE Barnes, AE Tomkinson, AR Lehmann, ADB Webster, T Lindahl
Cell, 1992cell.com
Two missense mutations occurring in different alleles of the DNA llgase I gene, encoding the
major DNA ligase in proliferating mammalian cells, were detected in a human flbroblast
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 …
Summary
Two missense mutations occurring in different alleles of the DNA llgase I gene, encoding the major DNA ligase in proliferating mammalian cells, were detected in a human flbroblast 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 Okaxaki fragments during lagging-strand DNA synthesis and the completion of DNA excision repair.
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