# IONIZING RADIATION INDUCED DNA DAMAGE AND REPAIR

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1987 · $172,210

## Abstract

The goal of this project is to increase our understanding of how
ionizing radiation causes cancer, mutation and cell death by
elucidating the enzymology and genetics of mammalian X-ray-
induced DNA repair.  A direct approach for the development of
human genetics for the enzymes of repair of X-ray-induced DNA
repair is described.

This project will define the primary structure and genetics of
human and bovine enzymes required for repair of ionizing
radiation-induced DNA damage.  Bovine tissue (calf thymus) will
be used as a source of preparation of homogeneous enzymes for
amino acid sequencing and antibody production.  The cDNA
sequences coding for repair enzymes will be selected from lambda
gt11 libraries by immunoscreening with rabbit anti-enzyme
antibodies or from lambda gt10 libraries by screening with mixed
oligonucleotides.  Once the cDNA for the bovine enzyme is
obtained the human cDNA will be selected from lambda gt10 or
lambda gt11 libraries through its nucleic acid homology or
immunologic cross reactivity, respectively.

Apurinic endonuclease has been chosen as the initial target for
cloning in this program for the following reasons; 1) Apurinic sites
in DNA are known to mutagenic (and possibly carcinogenic) 2)
apurinic sites are common to many types of DNA damage and
repair including X-rays 3) the issue of whether a single gene or
multiple mammalian genes code for AP endonuclease is
unresolved 4) the requirements for this approach have been
fulfilled a) homogeneous enzyme b) amino-acid sequence data c)
antibody probes and d) cDNA libraries for the tissue of origin are
all available.

Knowledge of the primary structure of the enzymes of X-ray
induced DNA repair will be useful in understanding how such
enzymes recognize damaged DNA, the sequence of events during
repair and how failures of repair might lead to the biological
effects of X-rays.  The availability of molecular probes for these
genes will allow studies of their role in the inherited defects of
DNA repair such as ataxia telangiectasia and in the susceptibility
of individuals and tumors to X-rays effects.

## Key facts

- **NIH application ID:** 3173344
- **Project number:** 2R01CA035767-04
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** WILLIAM D HENNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $172,210
- **Award type:** 2
- **Project period:** 1984-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173344

## Citation

> US National Institutes of Health, RePORTER application 3173344, IONIZING RADIATION INDUCED DNA DAMAGE AND REPAIR (2R01CA035767-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173344. Licensed CC0.

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