4.8 Article

AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation

Journal

ONCOGENE
Volume 24, Issue 38, Pages 5791-5798

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1208746

Keywords

AID; hypermutation; translocation; Burkitt's lymphoma

Funding

  1. NIEHS NIH HHS [R01 ES13192] Funding Source: Medline
  2. NIGMS NIH HHS [R01 GM65988, R01 GM039799, R01 GM041712, R01 GM065988, R37 GM21422, R01 GM39799] Funding Source: Medline

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Translocation and aberrant hypermutation of c-MYC are common in B-cell lymphomas. Activation-induced Cytidine Deaminase (AID) initiates switch recombination and somatic hypermutation in B cells by targeted deamination of transcribed genes. We show that transcription of the immunoglobulin S regions and c-MYC results in formation of similar DNA structures, 'G-loops', which contain a cotranscriptional RNA: DNA hybrid on the C-rich strand and single-stranded regions and G4 DNA on the G-rich strand. AID binds specifically to G-loops within transcribed S regions and c-MYC, and G-loops in c-MYC map to the regions associated with translocation breakpoints and aberrant hypermutation in B-cell lymphomas. Aberrant targeting of AID to DNA structures formed upon c-MYC transcription may therefore contribute to the genetic instability of c-MYC in B-cell malignancies.

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