TY - JOUR
T1 - 53BP1 is required for class switch recombination
AU - Ward, Irene M.
AU - Reina-San-Martin, Bernardo
AU - Olaru, Alexandru
AU - Minn, Kay
AU - Tamada, Koji
AU - Lau, Julie S.
AU - Cascalho, Marilia
AU - Chen, Lieping
AU - Nussenzweig, Andre
AU - Livak, Ferenc
AU - Nussenzweig, Michel C.
AU - Chen, Junjie
PY - 2004/5/24
Y1 - 2004/5/24
N2 - 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.
AB - 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.
KW - ATM
KW - DNA repair
KW - H2AX
KW - NHEJ
KW - V(D)J recombination
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U2 - 10.1083/jcb.200403021
DO - 10.1083/jcb.200403021
M3 - Article
C2 - 15159415
AN - SCOPUS:2542463148
SN - 0021-9525
VL - 165
SP - 459
EP - 464
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -