Regulation of activation-induced cytidine
deaminase DNA deamination activity in B-cells
Uttiya Basu*, Andrew Franklin*, Bjoern Schwer*, Hwei-Ling Cheng*, Jayanta Chaudhuri§ and
Frederick W. Alt*1
*Howard Hughes Medical Institute, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, U.S.A., Department of Genetics, Harvard Medical
School, 77 Avenue Louis Pasteur, NRB 0330, Boston, MA 02115, U.S.A., Immune Disease Institute, 800 Huntington Avenue, Boston, MA 02115, U.S.A., and
§Memorial Sloan Kettering Cancer Center, Immunology Program, New York, NY 10021, U.S.A.
Human and mouse Ig genes are diversified in mature B-cells by distinct processes known as Ig heavy-
chain CSR (class switch recombination) and Ig variable-region exon SHM (somatic hypermutation).
These DNA-modification processes are initiated by AID (activation-induced cytidine deaminase), a DNA
cytidine deaminase predominantly expressed in activated B-cells. AID is post-transcriptionally regulated
via multiple mechanisms, including microRNA regulation, nucleocytoplasmic shuttling, ubiquitination and
phosphorylation. Among these regulatory processes, AID phosphorylation at Ser38
has been a focus of
particularly intense study and debate. In the present paper, we discuss recent biochemical and mouse
genetic studies that begin to elucidate the functional significance of AID Ser38