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NYU School of Medicine pathology researchers solve another mystery in B lymphocyte development
Date:5/21/2009

e in the development of the immune system," says Skok. "But because it entails the repeated cutting and joining of DNA gene segments, it carries a risk of translocation."

Skok says that given the deleterious consequences, it is essential that B and T cells tightly regulate the recombinase, the accessibility of substrates for RAG cleavage, and the activities of the DNA damage response and repair machineries. Skok and researchers propose that homologous pairing of alleles undergoing recombination has a number of functions: (i) To protect genomic stability by ensuring that broken ends are aligned with homologous alleles rather than in contact with other loci. (ii) To provide a means for repair proteins recruited to sites of DSBs to act in trans on the uncleaved allele to prevent simultaneous cleavage on the latter. (iii) To ensure sequential recombination of individual alleles to help maintain allelic exclusion. In this sense homologous pairing of Ig alleles is analogous to pairing of X chromosomes which has an important role in X inactivation in developing female cells. The data suggest that in parallel with X inactivation, homologous pairing of Ig loci contributes to allelic exclusion by ensuring that only one allele is targeted for recombination at any time.


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Contact: Dorie Klissas
dorie.klissas@nyumc.org
212-404-3555
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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