Cells from an Immunodeficient Patient (46BR) with a Defect in DNA Ligation Are Hypomutable but Hypersensitive to the Induction of Sister Chromatid Exchanges

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1985 Apr 1

PMID 3856882

Citations 27

Authors

L M Henderson

C F Arlett

S A HARCOURT

A R Lehmann

B C Broughton

Affiliations

Soon will be listed here.

Abstract

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 a 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.

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