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Publication : RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci.

First Author  Hewitt SL Year  2009
Journal  Nat Immunol Volume  10
Issue  6 Pages  655-64
PubMed ID  19448632 Mgi Jnum  J:149451
Mgi Id  MGI:3848557 Doi  10.1038/ni.1735
Citation  Hewitt SL, et al. (2009) RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol 10(6):655-64
abstractText  Coordinated recombination of homologous antigen receptor loci is thought to be important for allelic exclusion. Here we show that homologous immunoglobulin alleles pair in a stage-specific way that mirrors the recombination patterns of these loci. The frequency of homologous immunoglobulin pairing was much lower in the absence of the RAG-1-RAG-2 recombinase and was restored in Rag1-/- developing B cells with a transgene expressing a RAG-1 active-site mutant that supported DNA binding but not cleavage. The introduction of DNA breaks on one immunoglobulin allele induced ATM-dependent repositioning of the other allele to pericentromeric heterochromatin. ATM activated by the cleaved allele acts in trans on the uncleaved allele to prevent biallelic recombination and chromosome breaks or translocations.
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