title: Close proximity to Igh is a contributing factor to AID-mediated translocations.
abstract: 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.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Rocha
authors.forename: Mariann
authors.initials: M
authors.lastname: Micsinai
authors.forename: JungHyun Rachel
authors.initials: JR
authors.lastname: Kim
authors.forename: Susannah L
authors.initials: SL
authors.lastname: Hewitt
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Souza
authors.forename: Thomas
authors.initials: T
authors.lastname: Trimarchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Strino
authors.forename: Fabio
authors.initials: F
authors.lastname: Parisi
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.forename: Jane A
authors.initials: JA
authors.lastname: Skok
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D050438:Genes, Immunoglobulin Heavy Chain; D042822:Genomic Instability; D017578:Immunoglobulin Class Switching; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D027041:Somatic Hypermutation, Immunoglobulin; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase