# MOLECULAR BASIS OF DNA REPAIR DEFICIENCY IN XERODERMA PI

> **NIH NIH R01** · STANFORD UNIVERSITY · 1987 · $218,833

## Abstract

The long-term objective of this project is to understand the molecular
basis of DNA repair deficiency in xeroderma pigmentosum (XP).  The overall
experimental strategy is to simplify the analysis by using agents such as
UV that produce only a few types of lesions, using specific assays for each
of these lesions, and using defined DNA sequences as substrates for repair
so that the processing of damage can be analyzed at the molecular level.

The following three experimental approaches and specific aims are planned:

(1) We have discovered that XP cells from complementation group C exhibit
an intracellular heterogeneity in the repair of DNA containing pyrimidine
dimers.  Some regions of the genome are repaired normally while others are
relatively inaccessible to repair.  We plan to analyze this response to
determine what distinguishes repairable from non-repairable regions, using
the methodology we have developed to isolate the repaired "domains."  We
will determine whether such heterogeneity is also a characteristic of other
XP complementation groups.

(2) Having obtained the first monoclonal antibody specific for thymine
glycol in DNA we will use it to study the repair and relative biological
significance of thymine glycol in normal and XP cells.  We plan to prepare
additional monoclonal antibodies and to use them as highly sensitive,
specific assays for pyrimidine dimers and other well-defined
photoproducts.  Results obtained from immunological assays will be compared
to those obtained using specific endonucleases to detect lesions and their
distribution in the genome.

(3) We will use defined chimeric plasmids to probe specific features of DNA
repair in XP cells.  We have found that 254 nm UV doses below 200 J/m
squared enhance the transformation efficiency of pSV2-gpt while doses above
1000 J/m squared cause a decrease which is more pronounced in XP-A than in
normal cells.  We will determine the nature of the inactivating lesions and
the cellular events that underly reactivation in normal cells.

This research should contribute substantially to our understanding of the
basis for DNA repair deficiency in XP and will also result in availability
of new, sensitive probes for the analysis of damage and repair in human
cells.

## Key facts

- **NIH application ID:** 3173325
- **Project number:** 5R01CA035744-04
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** PHILIP COURTLAND HANAWALT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $218,833
- **Award type:** 5
- **Project period:** 1984-05-01 → 1988-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173325

## Citation

> US National Institutes of Health, RePORTER application 3173325, MOLECULAR BASIS OF DNA REPAIR DEFICIENCY IN XERODERMA PI (5R01CA035744-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173325. Licensed CC0.

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