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 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.
Ward
Irene M
IM
1306 Guggenheim, Mayo Clinic, 200 First St., SW, Rochester, MN 55905, USA.
Reina-San-Martin
Bernardo
B
Olaru
Alexandru
A
Minn
Kay
K
Tamada
Koji
K
Lau
Julie S
JS
Cascalho
Marilia
M
Chen
Lieping
L
Nussenzweig
Andre
A
Livak
Ferenc
F
Nussenzweig
Michel C
MC
Chen
Junjie
J
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D006657:Histones / Q000172:deficiency / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D025521:Tumor Suppressor Proteins
D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C092537:Ifi202b protein, mouse; C576325:Atm protein, mouse; C475961:gamma-H2AX protein, mouse