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Mol Cell ; 47(6): 873-85, 2012 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-22864115

RESUMO

Class switch recombination (CSR) has the potential to generate genomic instability in B cells as activation-induced cytidine deaminase (AID), which mediates this process, is known to target many sites outside Igh. Nonetheless we do not fully understand what factors influence AID targeting genome-wide. Given that errors in CSR can lead to dangerous, oncogenic chromosomal translocations it is important to identify the elements that determine which genes are at risk of being "hit" and could be involved in aberrant rearrangements. Here we have investigated the influence of nuclear organization in determining "off-target" activity and the choice of fusion partners. Our studies indicate that the vast majority of known AID-mediated Igh translocation partners are found in chromosomal domains that contact this locus during class switching. Further, these interaction domains can be used to identify other genes that are hit by AID.


Assuntos
Linfócitos B/citologia , Citidina Desaminase/metabolismo , Genes de Cadeia Pesada de Imunoglobulina , Switching de Imunoglobulina , Translocação Genética , Animais , Linfócitos B/metabolismo , Citidina Desaminase/genética , Instabilidade Genômica , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Hipermutação Somática de Imunoglobulina
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