# Ajuba, a novel regulator of the ATR response in human cells.

> **NIH NIH SC3** · HUNTER COLLEGE · 2020 · $117,000

## Abstract

The ATR-dependent DNA damage response (DDR) is essential for genome integrity and constitutes
an important tumor suppressive system. DNA replication stress has been linked to cellular
transformation, and represents some of the early events leading to tumorigenesis in mammals. Our
work has centered on proteins that are part of the `Zyxin' LIM family, characterized by the presence of
tandem LIM domains at their C terminus, which we found were important for the repression of the
DNA damage response in human cells. Specifically, we have discovered that Ajuba is essential for
efficient repression of the ATR pathway in unperturbed cells. Depletion of Ajuba leads to activation of
ATR, followed by a potent apoptotic response.
We have discovered that Ajuba associates with the RPA complex, itself central to the ATR activation
pathway, and have detected a direct interaction in vitro between Ajuba and the RPA70 subunit.
RPA70 is composed of OB oligonucleotide/oligosaccharide-binding (OB) folds essential for single
strand DNA binding and assembly of the ATR activation complex. Based on these observations, we
hypothesize that Ajuba is an important repressor of inappropriate ATR activation in S phase through a
direct interaction with RPA70. We are proposing to study in detail the direct contacts between Ajuba
and RPA, and to analyze the significance of this interaction in human cells. Our results are expected
to improve our understanding of the regulation of the DNA damage response in human cells, itself
implicated in early events in cellular transformation and cancer.

## Key facts

- **NIH application ID:** 9954094
- **Project number:** 5SC3GM127157-03
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** Diego Loayza
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $117,000
- **Award type:** 5
- **Project period:** 2018-07-12 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954094

## Citation

> US National Institutes of Health, RePORTER application 9954094, Ajuba, a novel regulator of the ATR response in human cells. (5SC3GM127157-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954094. Licensed CC0.

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