AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation.
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.
Duquette
Michelle L
ML
Department of Biochemistry, University of Washington Medical School, Seattle, 98195-7650, USA.
Pham
Phuong
P
Goodman
Myron F
MF
Maizels
Nancy
N
D000818:Animals; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D016259:Genes, myc; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004277:DNA, Single-Stranded; D007136:Immunoglobulins; D012313:RNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase