# Role of XPD in DNA Damage Response Pathway Choice

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $388,181

## Abstract

PROJECT SUMMARY. Role of XPD in DNA Damage Response Pathway Choice
 The DNA damage response has evolved to protect the integrity of the human genome against the potentially
devastating effects of endogenous and exogenous genotoxins. A successful DNA damage response occurs due
to well-orchestrated crosstalk between pathways within the network. For instance, an intricate balance between
DNA repair and apoptosis minimizes the likelihood of genomic instability, which can lead to mutagenesis and
ultimately to disease. Although the regulatory mechanism and signaling pathways controlling DNA repair and
apoptosis are well characterized, the driving forces responsible for making the ultimate choice between DNA
repair and apoptosis in response to genotoxic stress remain unclear. The overall goal is to understand the
mechanisms involved in triggering the appropriate reaction at the intersection of the nucleotide excision repair
(NER) and apoptotic pathways.
 The NER pathway occupies an important position in the recognition and repair of a wide array of helix-
distorting lesions, including formation of triplex structures and lesions generated by chemotherapeutic agents.
Recent work from our group has discovered that the NER protein, XPD occupies a central role in triggering p53-
independent apoptosis in response to helix-distorting DNA damage via phosphorylation of the H2AX tyrosine142
residue. In Aim 1, we will determine how XPD tyrosine phosphorylation functions as a signaling mechanism to
mediate DNA repair-apoptosis pathway choice. In Aim 2, we will determine whether XPD’s role in cell fate
decisions is linked to its molecular properties essential for repair, transcription, and apoptosis. The proposed
work is highly significant because imbalance between pathways within the DNA damage response network can
eventually contribute to the etiology of human diseases.

## Key facts

- **NIH application ID:** 10531035
- **Project number:** 2R01GM126211-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Faye A Rogers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,181
- **Award type:** 2
- **Project period:** 2018-03-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10531035

## Citation

> US National Institutes of Health, RePORTER application 10531035, Role of XPD in DNA Damage Response Pathway Choice (2R01GM126211-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10531035. Licensed CC0.

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