This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lehmann, A. R. Articles by Lindahl, T. Search for Related Content PubMed PubMed Citation Articles by Lehmann, A. R. Articles by Lindahl, T.

Relation between the Human Fibroblast Strain 46BR and Cell Lines Representative of Bloom's Syndrome¹

MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR [A. R. L., B. C. B., M. R. J., H. S., S. A. H., C. F. A.], and Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts EN6 3LD [A. E. W., T. L.], United Kingdom

46BR is a human fibroblast strain derived from an immunodeficient young female of stunted growth. The diploid fibroblasts as well as a Simian Virus 40-transformed cell line are hypersensitive to killing by many DNA-damaging agents, exhibit a slightly increased level of spontaneous sister chromatid exchange, and show a defect in DNA ligation in vivo. 46BR is now shown to have abnormal DNA ligase I and is similar in this regard to cell lines derived from Bloom's syndrome patients. In a direct comparison, both 46BR and several Bloom's syndrome lines were found to be hypersensitive to the cytotoxic effect of simple alkylating agents, 46BR being more markedly sensitive. Bloom's syndrome lines do not exhibit the strong delay in joining of Okazaki fragments during DNA replication characteristic of 46BR. The cell line 46BR probably has a mutation in the gene encoding DNA ligase I different from those occurring in classical cases of Bloom's syndrome.

¹ This investigation was supported in part by EC [Grant B16.0142.UK(H)].

² To whom requests for reprints should be addressed, at ICRF Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.

Received 3/28/88. Revised 7/20/88. Accepted 8/17/88.

This article has been cited by other articles:

				A. Lopez Castel, A. E. Tomkinson, and C. E. Pearson CTG/CAG Repeat Instability Is Modulated by the Levels of Human DNA Ligase I and Its Interaction with Proliferating Cell Nuclear Antigen: A DISTINCTION BETWEEN REPLICATION AND SLIPPED-DNA REPAIR J. Biol. Chem., September 25, 2009; 284(39): 26631 - 26645. [Abstract] [Full Text] [PDF]

				W. Song, D. S. Levin, J. Varkey, S. Post, V. P. Bermudez, J. Hurwitz, and A. E. Tomkinson A Conserved Physical and Functional Interaction between the Cell Cycle Checkpoint Clamp Loader and DNA Ligase I of Eukaryotes J. Biol. Chem., August 3, 2007; 282(31): 22721 - 22730. [Abstract] [Full Text] [PDF]

				C. Harrison, A.-M. Ketchen, N. J. Redhead, M. J. O'Sullivan, and D. W. Melton Replication Failure, Genome Instability, and Increased Cancer Susceptibility in Mice with a Point Mutation in the DNA Ligase I Gene Cancer Res., July 15, 2002; 62(14): 4065 - 4074. [Abstract] [Full Text] [PDF]

				U. Lakshmipathy and C. Campbell Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity Nucleic Acids Res., February 1, 2001; 29(3): 668 - 676. [Abstract] [Full Text] [PDF]

				F. X. Mahon, M. W. N. Deininger, B. Schultheis, J. Chabrol, J. Reiffers, J. M. Goldman, and J. V. Melo Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance Blood, August 1, 2000; 96(3): 1070 - 1079. [Abstract] [Full Text] [PDF]

				N. Nicolas, D. Moshous, M. Cavazzana-Calvo, D. Papadopoulo, R. de Chasseval, F. Le Deist, A. Fischer, and J.-P. de Villartay A Human Severe Combined Immunodeficiency (SCID) Condition with Increased Sensitivity to Ionizing Radiations and Impaired V(D)J Rearrangements Defines a New DNA Recombination/Repair Deficiency J. Exp. Med., August 17, 1998; 188(4): 627 - 634. [Abstract] [Full Text] [PDF]

				R. Mossi, E. Ferrari, and U. Hubscher DNA Ligase I Selectively Affects DNA Synthesis by DNA Polymerases delta  and epsilon  Suggesting Differential Functions in DNA Replication and Repair J. Biol. Chem., June 5, 1998; 273(23): 14322 - 14330. [Abstract] [Full Text] [PDF]

				V. J. Mackenney, D. E. Barnes, and T. Lindahl Specific Function of DNA Ligase I in Simian Virus 40DNA Replication by Human Cell-free Extracts Is Mediated by the Amino-terminal Non-catalytic Domain J. Biol. Chem., April 25, 1997; 272(17): 11550 - 11556. [Abstract] [Full Text] [PDF]

				I. Husain, A. E. Tomkinson, W. A. Burkhart, M. B. Moyer, W. Ramos, Z. B. Mackey, J. M. Besterman, and J. Chen Purification and Characterization of DNA Ligase III from Bovine Testes J. Biol. Chem., April 21, 1995; 270(16): 9683 - 9690. [Abstract] [Full Text] [PDF]