TY - JOUR
T1 - C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion
AU - Barreto, Vasco
AU - Reina-San-Martin, Bernardo
AU - Ramiro, Almudena R.
AU - McBride, Kevin M.
AU - Nussenzweig, Michel C.
N1 - Funding Information:
We are indebted to members of the Nussenzweig laboratory, F. Papavasiliou, and T. Honjo, for discussions; K. Velinzon for cell sorting; J.M. Buerstedde for DT40 cells; and P. McDonnell for the ER template. This work was supported in part by grants from the US National Institutes of Health to M.C.N. M.C.N. is a Howard Hughes Medical Institute (HHMI) Investigator, V.B. is a fellow of the Fundação para a Ciência e Tecnologia (Portugal), B.R.S.M. is an HHMI postdoctoral associate, A.R.R. is a fellow of the Ministerio de Educacion, Cultura y Deporte (Spain), and K.M.M. is supported by a fellowship from the NIH.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Class-switch recombination (CSR), somatic hypermutation (SHM), and antibody gene conversion are distinct DNA modification reactions, but all are initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. Here we describe a mutant form of AID that catalyzes SHM and gene conversion but not CSR. When expressed in E. coli, AIDΔ189-198 is more active in catalyzing cytidine deamination than wild-type AID. AIDΔ189-198 also promotes high levels of gene conversion and SHM when expressed in eukaryotic cells, but fails to induce CSR. These results underscore an essential role for the C-terminal domain of AID in CSR that is independent of its cytidine deaminase activity and that is not required for either gene conversion or SHM.
AB - Class-switch recombination (CSR), somatic hypermutation (SHM), and antibody gene conversion are distinct DNA modification reactions, but all are initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. Here we describe a mutant form of AID that catalyzes SHM and gene conversion but not CSR. When expressed in E. coli, AIDΔ189-198 is more active in catalyzing cytidine deamination than wild-type AID. AIDΔ189-198 also promotes high levels of gene conversion and SHM when expressed in eukaryotic cells, but fails to induce CSR. These results underscore an essential role for the C-terminal domain of AID in CSR that is independent of its cytidine deaminase activity and that is not required for either gene conversion or SHM.
UR - https://www.scopus.com/pages/publications/0141992113
U2 - 10.1016/S1097-2765(03)00309-5
DO - 10.1016/S1097-2765(03)00309-5
M3 - Article
C2 - 14536088
AN - SCOPUS:0141992113
SN - 1097-2765
VL - 12
SP - 501
EP - 508
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -