# Role of TRF2 in DNA recombination

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $307,000

## Abstract

Antibody (immunoglobulin, Ig) class switch recombination (CSR) is an essential mechanism for the
diversification of humoral immune response through efficient generation of antibody isotypes that mediate
elimination of pathogens. CSR is a programmed deletional recombination event between DNA double strand
breaks in the Ig heavy chain gene locus (Igh). These DNA breaks are initiated by the mutagenic enzyme,
activation-induced cytidine deaminase (AID), which preferentially deaminates the Igh genes but also exhibits
‘off-target’ activity in non-Ig genes including proto-oncogenes. Hence, DNA breaks initiated by AID in off-target
regions of the genome lead to aberrant chromosome translocations between the Igh locus and oncogenes if
not correctly repaired. Indeed, such genomic aberrations are a hallmark of B cell malignancies. Accordingly the
goal of our research proposal is to characterize novel molecular mechanisms we have identified that regulate
the repair of DNA lesions initiated by AID during CSR. We recently discovered that the telomeric protein TRF2,
which is essential for protecting chromosome ends from DNA repair activity, is also needed for CSR. We
hypothesize that TRF2 is essential for the activity of DNA repair proteins involved in the processing of DNA
breaks initiated by AID during class switch recombination. Here we propose to extend our studies to identify
and characterize the molecular mechanisms utilized by TRF2 to control the CSR via the following specific
aims:
1. Determine the DNA repair proteins regulated by TRF2 during class switching.
2. Determine the molecular mechanisms used by TRF2 to control DNA repair during class switching.
3. Elucidate the mechanism by which TRF2 inhibits the formation of Igh-cmyc translocations.
Taken together, these studies will provide specific details into a novel mechanism that regulates immune
diversification in B cells and the maintenance of the genome stability during AID activation.

## Key facts

- **NIH application ID:** 9852451
- **Project number:** 5R01GM121595-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Ramiro Ernesto Verdun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $307,000
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852451

## Citation

> US National Institutes of Health, RePORTER application 9852451, Role of TRF2 in DNA recombination (5R01GM121595-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852451. Licensed CC0.

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