The catalytic subunit of DNA-protein kinase (DNA-PKcs) is not required for Ig class-switch recombination.
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.
Kiefer
Kerstin
K
Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Oshinsky
Jennifer
J
Kim
Jiyoon
J
Nakajima
Pamela B
PB
Bosma
Gayle C
GC
Bosma
Melvin J
MJ
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D001947:Breeding; D020134:Catalytic Domain; D002452:Cell Count; D051747:DNA-Activated Protein Kinase / Q000172:deficiency / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D005434:Flow Cytometry; D005838:Genotype; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes
D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse