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Cells from an immunodeficient patient (46BR) with a defect in DNA ligation are hypomutable but hypersensitive to the induction of sister chromatid exchanges

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
; ; ; ;
A fibroblast cell strain, 46BR, derived from an immunodeficient patient is hypersensitive to the lethal effects of a wide range of DNA-damaging agents. It is also defective in strand-break rejoining after treatment with dimethyl sulfate and UV light. The present study shows that the cells have a defect in joining Okazaki-type fragments during DNA replication, supporting the interpretation that the basic defect is in ligation of DNA strands. The baseline level of sister chromatid exchange is slightly higher than in normal cells but it does not approach that of Bloom's syndrome or dyskeratosis congenita cells. Sensitivity to the induction of sister chromatid exchange and the hypersensitivity to the lethal effects of a set of DNA-damaging agents are correlated, implying that the basic defect influences both end points in similar manner. No 6-thioguanine-resistant mutants could be induced by either ..gamma..- or UV-irradiation in these cells, suggesting that error-prone repair pathways for damage induced by these agents may contain a common ligation step in human cells.
Research Organization:
Univ. of Sussex, Brighton, England
OSTI ID:
6377676
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:7; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHROMOSOMAL ABERRATIONS
COBALT 60
COBALT ISOTOPES
CONNECTIVE TISSUE CELLS
DNA REPAIR
ELECTROMAGNETIC RADIATION
ENZYMES
EXTREME ULTRAVIOLET RADIATION
FIBROBLASTS
GAMMA RADIATION
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
IMMUNOSUPPRESSION
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LIGASES
MINUTES LIVING RADIOISOTOPES
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOISOTOPES
RECOVERY
REPAIR
SISTER CHROMATID EXCHANGES
SOMATIC CELLS
STRAND BREAKS
ULTRAVIOLET RADIATION
YEARS LIVING RADIOISOTOPES