title: Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes.
abstract: The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed mechanisms of the DNA strand cleavage in SHM and CSR are still largely unknown. Recently, the apurinic/apyrimidinic endonucleases, Apex1 and Apex2, were reported to be involved in the DNA cleavage step of CSR. Here, we examined the role of Apex2 in SHM using Apex2-deficient mice and found that the Apex2 deficiency caused a drastic reduction in the frequency of SHM and the number of mutations per mutated clone without affecting the pattern of base substitution. These results suggest that Apex2 may play a critical role in SHM through its 3'-5' exonuclease activity. Unexpectedly, the efficiency of CSR was not reduced in Apex2-deficient B cells. In addition, Apex1 knockdown in CH12F3-2 B lymphoma cells did not affect the CSR frequency, suggesting that neither Apex1 nor Apex2 plays a major role in CSR.
authors: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Kyoto, Japan.
authors: Zahra
authors: Z
authors: Sabouri
authors: Il-Mi
authors: IM
authors: Okazaki
authors: Reiko
authors: R
authors: Shinkura
authors: Nasim
authors: N
authors: Begum
authors: Hitoshi
authors: H
authors: Nagaoka
authors: Daisuke
authors: D
authors: Tsuchimoto
authors: Yusaku
authors: Y
authors: Nakabeppu
authors: Tasuku
authors: T
authors: Honjo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004720:Endonucleases / Q000235:genetics / Q000502:physiology*; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064251:Multifunctional Enzymes; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
chemical_list: D064251:Multifunctional Enzymes; C476886:Apex2 protein, mouse; D004720:Endonucleases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase