# Mechanistic Elucidation of Class Switch Recombination and Somatic Hypermutation

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $531,000

## Abstract

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 single proteins can coordinate both
DSB formation and mediate end-joining to efficiently generate and repair DSBs. We test the hypothesis that
the nucleosomal remodeling protein CHD4 co-ordinates generation and repair of Igh DSBs (aim 1) and the C-
terminus of AID mediates efficient DNA repair of Igh DSBs (aim 2). Successful completion of the experiments
will have far reaching implications in our understanding of both B cell immunity and B cell lymphomas.

## Key facts

- **NIH application ID:** 10348783
- **Project number:** 5R01AI072194-12
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jayanta Chaudhuri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $531,000
- **Award type:** 5
- **Project period:** 2009-07-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348783

## Citation

> US National Institutes of Health, RePORTER application 10348783, Mechanistic Elucidation of Class Switch Recombination and Somatic Hypermutation (5R01AI072194-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10348783. Licensed CC0.

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