53BP1 is required for class switch recombination

Irene M. Ward, Bernardo Reina-San-Martin, Alexandru Olaru, Kay Minn, Koji Tamada, Julie S. Lau, Marilia Cascalho, Lieping Chen, Andre Nussenzweig, Ferenc Livak, Michel C. Nussenzweig, Junjie Chen

Research output: Contribution to journalArticle

Abstract

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" non-homologous 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.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalJournal of Cell Biology
Volume165
Issue number4
DOIs
StatePublished - May 24 2004
Externally publishedYes

Fingerprint

Genetic Recombination
Cell Cycle Checkpoints
V(D)J Recombination
Gene Conversion
Double-Stranded DNA Breaks
Homologous Recombination
DNA Repair
DNA Damage
Phenotype
DNA
Neoplasms

Keywords

  • ATM
  • DNA repair
  • H2AX
  • NHEJ
  • V(D)J recombination

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ward, I. M., Reina-San-Martin, B., Olaru, A., Minn, K., Tamada, K., Lau, J. S., ... Chen, J. (2004). 53BP1 is required for class switch recombination. Journal of Cell Biology, 165(4), 459-464. https://doi.org/10.1083/jcb.200403021

53BP1 is required for class switch recombination. / Ward, Irene M.; Reina-San-Martin, Bernardo; Olaru, Alexandru; Minn, Kay; Tamada, Koji; Lau, Julie S.; Cascalho, Marilia; Chen, Lieping; Nussenzweig, Andre; Livak, Ferenc; Nussenzweig, Michel C.; Chen, Junjie.

In: Journal of Cell Biology, Vol. 165, No. 4, 24.05.2004, p. 459-464.

Research output: Contribution to journalArticle

Ward, IM, Reina-San-Martin, B, Olaru, A, Minn, K, Tamada, K, Lau, JS, Cascalho, M, Chen, L, Nussenzweig, A, Livak, F, Nussenzweig, MC & Chen, J 2004, '53BP1 is required for class switch recombination', Journal of Cell Biology, vol. 165, no. 4, pp. 459-464. https://doi.org/10.1083/jcb.200403021
Ward IM, Reina-San-Martin B, Olaru A, Minn K, Tamada K, Lau JS et al. 53BP1 is required for class switch recombination. Journal of Cell Biology. 2004 May 24;165(4):459-464. https://doi.org/10.1083/jcb.200403021
Ward, Irene M. ; Reina-San-Martin, Bernardo ; Olaru, Alexandru ; Minn, Kay ; Tamada, Koji ; Lau, Julie S. ; Cascalho, Marilia ; Chen, Lieping ; Nussenzweig, Andre ; Livak, Ferenc ; Nussenzweig, Michel C. ; Chen, Junjie. / 53BP1 is required for class switch recombination. In: Journal of Cell Biology. 2004 ; Vol. 165, No. 4. pp. 459-464.
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