Abstract
Defective V(D)J rearrangement of immunoglobulin heavy or light chain (IgH or IgL) or class switch recombination (CSR) can initiate chromosomal translocations. The DNA-damage kinase ATM is required for the suppression of chromosomal translocations but ATM regulation is incompletely understood. Here, we show that mice lacking the ATM cofactor ATMIN in B cells (ATMIN(ΔB/ΔB)) have impaired ATM signaling and develop B cell lymphomas. Notably, ATMIN(ΔB/ΔB) cells exhibited defective peripheral V(D)J rearrangement and CSR, resulting in translocations involving the Igh and Igl loci, indicating that ATMIN is required for efficient repair of DNA breaks generated during somatic recombination. Thus, our results identify a role for ATMIN in regulating the maintenance of genomic stability and tumor suppression in B cells.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 587-600 |
| Number of pages | 14 |
| Journal | CANCER CELL |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 17 May 2011 |
Keywords
- Animals
- Antigens, CD19
- B-Lymphocytes
- Carrier Proteins
- Cell Cycle Proteins
- Cells, Cultured
- DNA Breaks
- DNA-Binding Proteins
- Gene Expression Regulation, Neoplastic
- Genes, Immunoglobulin Heavy Chain
- Genes, Immunoglobulin Light Chain
- Genomic Instability
- Immunoglobulin Class Switching
- Lymphoma, B-Cell
- Mice
- Mice, Inbred ICR
- Mice, Knockout
- Mice, Nude
- Nuclear Proteins
- Protein-Serine-Threonine Kinases
- Recombination, Genetic
- Signal Transduction
- Time Factors
- Tumor Suppressor Proteins