The Journal of Experimental Medicine
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Published online March 10, 2008
doi:10.1084/jem.20080356
The Journal of Experimental Medicine, Vol. 205, No. 3, 509-513
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Jolly et al.
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COMMENTARY

 Fixing DNA breaks during class switch recombination

Christopher J. Jolly, Adam J.L. Cook, and John P. Manis

C.J. Jolly is at Centenary Institute, The University of Sydney, Sydney NSW 2006, Australia
A.J.L. Cook is at UMR 218 Centre National de la Recherche Scientifique/Institut Curie, 75248 Paris, France
J.P. Manis is at Joint Program in Transfusion Medicine and Department of Laboratory Medicine, Children's Hospital Boston, and Department of Pathology, Harvard Medical School, Boston, MA 02115

CORRESPONDENCE J.P.M.: manis{at}enders.tch.harvard.edu


ABSTRACT
Immunoglobulin (Ig) class switch recombination (CSR) involves the breakage and subsequent repair of two DNA sequences, known as switch (S) regions, which flank IgH constant region exons. The resolution of CSR-associated breaks is thought to require the nonhomologous end-joining (NHEJ) DNA repair pathway, but the role of the NHEJ factor DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in this process has been unclear. A new study, in which broken IgH-containing chromosomes in switching B cells were visualized directly, clearly demonstrated that DNA-PKcs and, unexpectedly, the nuclease Artemis are involved in the resolution of switch breaks.


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DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination
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J. Exp. Med. 2008 205: 557-564. [Abstract] [Full Text] [PDF]





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