The Catalytic Subunit of DNA-protein Kinase (DNA-PKcs) is Not Required for Ig Class-switch Recombination
Overview
Affiliations
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.
The recent advances in non-homologous end-joining through the lens of lymphocyte development.
Wang X, Lee B, Zha S DNA Repair (Amst). 2020; 94:102874.
PMID: 32623318 PMC: 7885906. DOI: 10.1016/j.dnarep.2020.102874.
ATM, ATR and DNA-PKcs kinases-the lessons from the mouse models: inhibition ≠ deletion.
Menolfi D, Zha S Cell Biosci. 2020; 10:8.
PMID: 32015826 PMC: 6990542. DOI: 10.1186/s13578-020-0376-x.
Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination.
Crowe J, Shao Z, Wang X, Wei P, Jiang W, Lee B Proc Natl Acad Sci U S A. 2018; 115(34):8615-8620.
PMID: 30072430 PMC: 6112704. DOI: 10.1073/pnas.1808490115.
Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.
Hwang J, Alt F, Yeap L Microbiol Spectr. 2015; 3(1):MDNA3-0037-2014.
PMID: 26104555 PMC: 4481323. DOI: 10.1128/microbiolspec.MDNA3-0037-2014.
Zhang S, Zhang H, Yang T, Ying T, Yang P, Liu X Int J Biol Sci. 2014; 10(10):1138-49.
PMID: 25332688 PMC: 4202030. DOI: 10.7150/ijbs.10366.