# RNA-directed targeting of AID in immunity and genomic integrity

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $449,000

## Abstract

   
DESCRIPTION (provided by applicant): DNA double strand breaks (DSBs) constitute one of the most toxic lesions to occur in a cell. Unrepaired DSBs can either lead to cell death or can participate in chromosomal translocations that are hallmarks of many kinds of tumors, including lymphomas. Despite the toxicity associated with DSBs, during the immunoglobulin (Ig) gene diversification process of class switch recombination (CSR), DSBs are deliberately introduced into defined regions, called switch (S) regions, of the B cell genome, and a failure to introduce such DSBs leads to immunodeficiency syndromes. The DNA deaminase AID (activation induced cytidine deaminase) is essential for the generation of DSBs. While S regions (and the Ig gene associated variable region gene segments) are primary targets, AID has the potential to induce DSBs at non-Ig genes, including oncogenes. Such off-target DSBs are the major lesions behind the ontogeny of a large number of mature B cell lymphomas. Despite the relevance of AID targeting to both immunity and cancer, the molecular mechanisms underlying AID specificity are yet to be fully elucidated. We have now shown that noncoding RNA emanating from S regions act as molecular guides to recruit AID to S regions. This proposal tests the hypothesis that switch transcripts not only recruit AID to S regions to facilitate CSR but also sequester AID from other genomic regions to prevent collateral damage during B cell gene diversification. In aim 1, we test the notion that the RNA-guided recruitment of AID is critical fo CSR in vivo. In aim 2, we examine if RNA-guided AID recruitment serves to shelter the B cell genome from collateral AID-induced DNA damage. In aim 3, we design chimeric RNA molecules for ectopic targeting of AID. These studies will have far-reaching implications into our fundamental understanding of both immunity and how simple aberrations in the process could lead to B cell lymphomas.

## Key facts

- **NIH application ID:** 9851741
- **Project number:** 5R01AI124186-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jayanta Chaudhuri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,000
- **Award type:** 5
- **Project period:** 2016-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851741

## Citation

> US National Institutes of Health, RePORTER application 9851741, RNA-directed targeting of AID in immunity and genomic integrity (5R01AI124186-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851741. Licensed CC0.

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