This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The 'Activation Induced Deaminase' (AID-protein) is potentially involved in RNA editing in human lymphocytes. In search for possible interacting proteins, that could function in the assumed recruitment of AID to specific RNAs, we have employed MALDI-ion trap MS/MS analysis to identify proteins that are co-purified with flag/HA-tagged AID. We have also identified sites of phosphorylation on AID at a site that appears to play an important role in regulating AID activity.Activation-induced cytidine deaminase (AID) initiates Ig classswitch recombination and somatic hypermutation by producingU:G mismatches in DNA. These mismatches also have the potentialto induce DNA damage including double-stranded breaks andchromosome translocations; therefore, strict regulation of AID isimportant for maintaining genomic stability. In addition to transcriptionalregulation, it has been proposed that phosphorylationcan also modulate AID activity. Using a combination of MS andimmunochemical approaches we found that 515% of the AIDexpressed in activated B cells was phosphorylated at serine-38(p38AID). This form of AID was enriched in the chromatin fractionin activated B cells, suggesting a role for phosphorylation intargeting AID to DNA. Consistent with this idea, serine-38 toalanine mutant AID (AIDS38A) showed diminished somatic hypermutationactivity on artificial and physiological DNA targets. Weconclude that a small fraction of AID is phosphorylated in activatedB cells and that the modified form contributes disproportionatelyto hypermutation.
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