# Project 6:  Vpr subversion of DNA repair

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $301,972

## Abstract

P6. Abstract
The accessory protein Vpr facilitates HIV-1 replication in dividing T cells, ensuring orderly progression through
the HIV-1 life cycle. The most remarkable Vpr phenotype is induction of DNA damage checkpoint and cell cycle
arrest in G2/M phase, although the underlying details are the still elusive. There is compelling evidence that Vpr
interacts with several cellular proteins that recognize damaged DNA, targeting them for proteasomal degradation
via CRL4DCAF1 E3 ubiquitin ligase. While evident that, in principle, Vpr antagonism of DNA repair ultimately can
be of benefit to HIV-1, the full extent of Vpr-mediated subversion of cellular DNA repair is not known. In this
project, we propose to systematically explore the extent of Vpr's engagement with the DNA repair machinery,
focusing on DNA repair pathways that recognize and process “marks of damage”, introduced into HIV-1 cDNA
during reverse transcription. We aim to discover and validate other specific DNA repair protein(s) that are
targeted by Vpr, in particular those mediating the induction of DNA damage checkpoint and cell cycle arrest.
Further, we will biochemically, biophysically and structurally analyze the interactions between Vpr and the
already identified targets HLTF, MUS81-EME1, and hHR23A, as well as any new target(s) discovered in this
project. Overall, our studies will define the extent of Vpr-induced changes in cellular DNA repair, identify specific
DNA repair pathways/proteins targeted by Vpr, and structurally characterize the responsible CRL4DCAF1
E3/Vpr/target complexes.

## Key facts

- **NIH application ID:** 10219104
- **Project number:** 5P50AI150481-15
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ANGELA M. GRONENBORN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $301,972
- **Award type:** 5
- **Project period:** 2007-08-27 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219104

## Citation

> US National Institutes of Health, RePORTER application 10219104, Project 6:  Vpr subversion of DNA repair (5P50AI150481-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219104. Licensed CC0.

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