53BP1 Is Required for Class Switch Recombination

53BP1 participates early in the DNA damage response and is involved in cell cycle checkpoint control. Moreover, the phenotype of mice and cells deficient in 53BP1 suggests a defect in DNA repair (Ward et al., 2003b). Therefore, we asked whether or not 53BP1 would be required for the efficient repair...

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Bibliographic Details
Published in:The Journal of cell biology 2004-05, Vol.165 (4), p.459-464
Main Authors: Ward, Irene M., Bernardo Reina-San-Martin, Olaru, Alexandru, Minn, Kay, Tamada, Koji, Lau, Julie S., Cascalho, Marilia, Chen, Lieping, Nussenzweig, Andre, Livak, Ferenc, Nussenzweig, Michel C., Chen, Junjie
Format: Article
Language:English
Subjects:
Animals
Ataxia Telangiectasia Mutated Proteins
B lymphocytes
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Cycle Proteins
Cell Line
Cell lines
Cells
Cellular biology
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
DNA damage
DNA Damage - genetics
DNA Repair - genetics
DNA-Binding Proteins
Embryonic cells
Gene Expression Regulation - genetics
Gene Rearrangement - genetics
Histones - deficiency
Histones - genetics
Injuries
Intracellular Signaling Peptides and Proteins
Mice
Phosphoproteins
Plasmids
Polymerase chain reaction
Protein-Serine-Threonine Kinases - deficiency
Protein-Serine-Threonine Kinases - genetics
Recombination, Genetic - genetics
Rodents
Sequence Homology, Nucleic Acid
T lymphocytes
Thymocytes
Tumor Suppressor Proteins
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Summary:53BP1 participates early in the DNA damage response and is involved in cell cycle checkpoint control. Moreover, the phenotype of mice and cells deficient in 53BP1 suggests a defect in DNA repair (Ward et al., 2003b). Therefore, we asked whether or not 53BP1 would be required for the efficient repair of DNA double strand breaks. Our data indicate that homologous recombination by gene conversion does not depend on 53BP1. Moreover, 53BP1-deficient mice support normal V(D)J recombination, indicating that 53BP1 is not required for "classic" nonhomologous end joining. However, class switch recombination is severely impaired in the absence of 53BP1, suggesting that 53BP1 facilitates DNA end joining in a way that is not required or redundant for the efficient closing of RAG-induced strand breaks. These findings are similar to those observed in mice or cells deficient in the tumor suppressors ATM and H2AX, further suggesting that the functions of ATM, H2AX, and 53BP1 are closely linked.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200403021