AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching

Nature. 2001 Dec 6;414(6864):660-665. doi: 10.1038/414660a.


Class switch recombination (CSR) is a region-specific DNA recombination reaction that replaces one immunoglobulin heavy-chain constant region (Ch) gene with another. This enables a single variable (V) region gene to be used in conjunction with different downstream Ch genes, each having a unique biological activity. The molecular mechanisms that mediate CSR have not been defined, but activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is required for this reaction. Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (gamma-H2AX, also known as gamma-H2afx), which facilitate DNA double-strand break (DSB) repair, form nuclear foci at the Ch region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX-/- mice. Localization of Nbs1 and gamma-H2AX to the Igh locus during CSR is dependent on AID. In addition, AID is required for induction of switch region (S mu)-specific DNA lesions that precede CSR. These results place AID function upstream of the DNA modifications that initiate CSR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • BRCA1 Protein / physiology
  • Base Sequence
  • Cell Cycle
  • Cells, Cultured
  • Cloning, Molecular
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / physiology*
  • DNA
  • DNA Repair
  • DNA-Binding Proteins / physiology
  • Histones / physiology*
  • Immunoglobulin Class Switching / physiology*
  • Immunoglobulin Heavy Chains / genetics
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutagenesis*
  • Nuclear Proteins / physiology*
  • Rad51 Recombinase
  • Recombination, Genetic


  • BRCA1 Protein
  • DNA-Binding Proteins
  • Histones
  • Immunoglobulin Heavy Chains
  • Nuclear Proteins
  • DNA
  • Rad51 Recombinase
  • Rad51 protein, mouse
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase