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

doi:10.1016/0092-8674(92)90450-Q

Cell

Volume 69, Issue 3, 1 May 1992, Pages 495-503

https://doi.org/10.1016/0092-8674(92)90450-Q Get rights and content

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.

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^†: Present address: Department of Pathology, Southwestern Medical Center, University of Texas, Dallas, Texas 75235-9072.

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Cell

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

Abstract

J. Biol. Chem.

Genomics

J. Pediatr.

J. Biol. Chem.

Meth. Enzymol.

Mutat. Res.

Mutat. Res.

Anal. Biochem.

Biochim. Biophys. Acta

Mutat. Res.

Mutat. Res.

Prog. Nucl. Acids Res. Mol. Biol.

Exp. Cell Res.

Gene

Mutation Res.

J. Biol. Chem.

J. Biol. Chem.

Cell

Human DNA ligase I cDNA: cloning and functional expression in Saccharomyces cerevisiae

scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double strand break-related repair

Altered DNA ligase I activity in Bloom's syndrome cells

Nature

The CpG dinucleotide and human genetic disease

Hum. Genet.

Conditional-lethal deoxyribonucleic acid ligase mutant of Escherichia coli

J. Bacteriol.

DNA ligases from rat liver

Purification and partial characterisation of two molecular forms

Biochemistry

DNA Repair

The scid mutation in mice causes a general defect in DNA repair

Nature

Bloom's syndrome. IV. Sister-chromatid exchanges in lymphocytes

Am. J. Hum. Genet.

Ultraviolet light sensitivity and delayed DNA-chain maturation in Bloom's syndrome fibroblasts

Nature

A retarded rate of DNA chain growth in Bloom's syndrome fibroblasts

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