# Rad52-dependent recombination in response to replication stress

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $243,000

## Abstract

SUMMARY
Genomic instability, one of the hallmarks of cancer, is driven by replication stress. Replication stress can
result from oncogene activation, damage to the template strands, depletion of nucleotides, or from
physical impediments to progression of replication forks, such as non-canonical DNA structures or tightly
bound proteins. Homologous recombination (HR) at stalled or collapsed replication forks is important to
restart replication, but at the same time can be an additional source of genomic instability by promoting
chromosome rearrangements. Recent studies identified an unexpected role for Rad52 in facilitating DNA
synthesis in response to replication stress in human cells. Although Rad52 is essential for all HR in
budding yeast, its role in mammalian cells had seemed minor because mice lacking it are viable and
show only mild defects in HR. The finding that Rad52 is required for viability of BRCA2-deficient cells has
been interpreted as redundancy for mediating Rad51 filament assembly. However, the new studies
showing that Rad52-promoted DNA synthesis in response to replication stress is independent of Rad51
suggest a novel function for Rad52. Because Rad52 has emerged as potential therapeutic target for
BRCA-deficient tumors, it is important to understand its cellular functions. Here we apply the facile
genetics of budding yeast and new technologies to create a site-specific replication fork stall or collapse
to identify the mechanism for Rad52 dependent recombination in the context of replication stress. In the
first aim of the proposal, we will use Tus/Ter or Flp/FRT systems to induce a replication fork stall or
collapse, respectively, adjacent to a sensitive reporter to detect HR in dividing cells. We will determine
the requirements for Rad51 and Rad52 for Tus/Ter and Flp/FRT-stimulated recombination, and identify
recombination intermediates by two-dimensional gel electrophoresis. The role of converging forks in
suppressing HR at the Tus/Ter block will also be tested. The second aim addresses the role of Rad51
stabilization of stalled forks, nascent strand degradation and Pol32-dependent DNA synthesis for
Tus/Ter-induced recombination.
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## Key facts

- **NIH application ID:** 9894801
- **Project number:** 5R21ES030447-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Lorraine S Symington
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,000
- **Award type:** 5
- **Project period:** 2019-03-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894801

## Citation

> US National Institutes of Health, RePORTER application 9894801, Rad52-dependent recombination in response to replication stress (5R21ES030447-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894801. Licensed CC0.

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