Activation-induced cytidine deaminase-mediated sequence diversification is transiently targeted to newly integrated DNA substrates.
The molecular features that allow activation-induced cytidine deaminase (AID) to target Ig and certain non-Ig genes are not understood, although transcription has been implicated as one important parameter. We explored this issue by testing the mutability of a non-Ig transcription cassette in Ig and non-Ig loci of the chicken B cell line DT40. The cassette did not act as a stable long term mutation target but was able to be mutated in an AID-dependent manner for a limited time post-integration. This indicates that newly integrated DNA has molecular characteristics that render it susceptible to modification by AID, with implications for how targeting and mis-targeting of AID occurs.
Yang
Shu Yuan
SY
Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Fugmann
Sebastian D
SD
Gramlich
Hillary S
HS
Schatz
David G
DG
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D002460:Cell Line; D002645:Chickens; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D016254:Mutagenesis, Insertional; D009154:Mutation; D013379:Substrate Specificity / Q000502:physiology; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007136:Immunoglobulins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase