RNA-directed targeting of AID in immunity and cancer

ABSTRACT
Upon encountering antigens, mature B cells express activation induced cytidine deaminase (AID) and undergo
immunoglobulin heavy chain (Igh) class switch recombination (CSR) and somatic hypermutation (SHM). CSR
proceeds through the obligate generation of DNA double strand breaks (DSBs), which constitute one of the
most toxic lesions that can occur in a cell. A single unrepaired DSB can cause cell death or potentiate
chromosomal translocations that are hallmarks of many types of cancer, including lymphomas. Thus,
mechanisms that promote generation of DSBs and facilitate DSB repair are intergral to both immunity and
preservation of genomic integrity. In this proposal we test the notion that non-canonical DNA structures such
as G-quadruplexes target the DNA deaminase AID to the chromatin during CSR (aim 1) and that AID can
regulate expression of non-Ig genes to influence B cell responses (aim 2). Successful completion of the
experiments will have far reaching implications in our understanding of both B cell immunity and B cell
lymphomas.

Grant Number: 5R01AI124186-09
NIH Institute/Center: NIH
Principal Investigator: Jayanta Chaudhuri