APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination

作者：Xu Jianliang; Husain Afzal; Hu Wenjun; Honjo Tasuku^*; Kobayashi Maki

来源：Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(48): 17242-17247.

DOI：10.1073/pnas.1420221111/-/DCSupplemental

• class switch recombination
• somatic hypermutation
• DNA cleavage
• DNA synapse formation
• end processing

Activation-induced cytidine deaminase (AID) is essential for antibody diversification, namely somatic hypermutation (SHM) and class switch recombination (CSR). The deficiency of apurinic/apyrimidinic endonuclease 1 (Ape1) in CH12F3-2A B cells reduces CSR to similar to 20% of wild-type cells, whereas the effect of APE1 loss on SHM has not been examined. Here we show that, although APE1' s endonuclease activity is important for CSR, it is dispensable for SHM as well as IgH/c-myc translocation. Importantly, APE1 deficiency did not show any defect in AID-induced S-region break formation, but blocked both the recruitment of repair protein Ku80 to the S region and the synapse formation between S mu and S alpha. Knockdown of end-processing factors such as meiotic recombination 11 homolog (MRE11) and carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) further reduced the remaining CSR in Ape1-null CH12F3-2A cells. Together, our results show that APE1 is dispensable for SHM and AID-induced DNA breaks and may function as a DNA end-processing enzyme to facilitate the joining of broken ends during CSR.

• 出版日期2014-12-2