The catalytic subunit of DNA–protein kinase (DNA-PKcs) is not required for Ig class-switch recombination
- 20 February 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (8), 2843-2848
- https://doi.org/10.1073/pnas.0611359104
Abstract
The joining of DNA ends during Ig class-switch recombination (CSR) is thought to involve the same nonhomologous end-joining pathway as used in V(D)J recombination. However, we reported earlier that CSR can readily occur in Ig transgenic SCID mice lacking DNA-dependent protein kinase (DNA-PK) activity, a critical enzymatic activity for V(D)J recombination. We were thus led to question whether the catalytic subunit of DNA-PK (DNA-PKcs) is essential for CSR. To address this issue, we asked whether class switching to different Ig isotypes could occur in a line of Ig transgenic mice lacking detectable DNA-PKcs protein. The answer was affirmative. We conclude that joining of DNA ends during CSR does not require DNA-PKcs and can occur by an alternative repair pathway to that used for V(D)J recombination.Keywords
This publication has 55 references indexed in Scilit:
- DNA-PK autophosphorylation facilitates Artemis endonuclease activityThe EMBO Journal, 2006
- Artemis Phosphorylated by DNA-dependent Protein Kinase Associates Preferentially with Discrete Regions of ChromatinJournal of Molecular Biology, 2006
- MECHANISM AND CONTROL OF V(D)J RECOMBINATION AT THE IMMUNOGLOBULIN HEAVY CHAIN LOCUSAnnual Review of Immunology, 2006
- Staggered AID-dependent DNA double strand breaks are the predominant DNA lesions targeted to S in Ig class switch recombinationInternational Immunology, 2004
- DNA Ligase IV and XRCC4 Form a Stable Mixed Tetramer That Functions Synergistically with Other Repair Factors in a Cell-free End-joining SystemPublished by Elsevier BV ,2000
- Extended Duration of DH–JH Rearrangement in Immunoglobulin Heavy Chain Transgenic Mice: Implications for Regulation of Allelic ExclusionThe Journal of Experimental Medicine, 1999
- Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse.Proceedings of the National Academy of Sciences of the United States of America, 1996
- Expression of anti-DNA immunoglobulin transgenes in non-autoimmune miceNature, 1991
- The defect in murine severe combined immune deficiency: Joining of signal sequences but not coding segments in V(D)J recombinationCell, 1988
- Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genesCell, 1981