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X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining

  作者 Han, L; Mao, WF; Yu, KF  
  选自 期刊  Proceedings of the National Academy of Sciences of the United States of America;  卷期  2012年109-12;  页码  4604-4608  
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[摘要]DNA double-strand breaks (DSBs) are essential intermediates in Ig gene rearrangements: V(D)J and class switch recombination (CSR). In contrast to V(D) J recombination, which is almost exclusively dependent on nonhomologous end joining (NHEJ), CSR can occur in NHEJ-deficient cells via a poorly understand backup pathway (or pathways) often termed alternative end joining (A-EJ). Recently, several components of the single-strand DNA break (SSB) repair machinery, including XRCC1, have been implicated in A-EJ. To determine its role in A-EJ and CSR, Xrcc1 was deleted by targeted mutation in the CSR proficient mouse B-cell line, CH12F3. Here we demonstrate that XRCC1 deficiency slightly increases the efficiency of CSR. More importantly, Lig4 and XRCC1 double-deficient cells switch as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is dispensable for A-EJ in CH12F3 cells during CSR.

 
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