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- W2921752559 abstract "Abstract Activation-induced cytidine deaminase (AID) initiates DNA breakage in the variable (V) and switch (S) regions of the immunoglobulin gene, which results in somatic hypermutation (SHM) and class switch recombination (CSR), respectively. Apurinic/apyrimidinic endonuclease 1 (APE1) has been shown to be important for CSR, and is supposed to cleave at abasic sites when AID-dependently deaminated cytidine is removed by uracil DNA glycosylase. However, APE1 is unexpectedly dispensable for SHM in the S region and translocation between immunoglobulin heavy chain (IgH) and c-myc genes in the mouse B lymphoma cell line, CH12F3-2A. This suggested that APE1 is not involved in AID-dependent DNA breakage, but rather, in DNA repair. In order to investigate detailed molecular mechanisms underlying APE1’s involvement in CSR and SHM, we measured apurinic/apyrimidinic (AP) sites via aldehyde reactive probe labeling. Results indicated that the frequencies of AP sites in the S regions were not different between APE1−/−/−CH12F3-2A and wild-type CH12F3-2A cells. To carry out similar experiments in SHM of the V region, we generated an APE1 knockout (APE1−/−) human Burkitt’s lymphoma cell line, and compared SHM between APE1-proficient and -deficient BL2 lymphoma cells. SHM frequencies in the V regions of APE1−/−BL2 and APE1-proficient cells were also similar. Taken together, we showed that AID does not induce AP sites in the S region of the IgH gene, and that APE1 is not necessary for SHM in the V and S regions; however, it is required for DNA repair following DNA breakage in CSR." @default.
- W2921752559 created "2019-03-22" @default.
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- W2921752559 date "2019-03-16" @default.
- W2921752559 modified "2023-10-16" @default.
- W2921752559 title "Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene" @default.
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- W2921752559 doi "https://doi.org/10.1093/intimm/dxz028" @default.
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