# MAPPING CARCINOGEN BINDING SITES ON GENES

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1988 · $210,167

## Abstract

One objective of this proposal is to use photochemical methods
which we have developed to map carcinogen and mutagen sites on DNA,
and to use those data to establish how binding is coupled to DNA
structure variation, at one base resolution.  We are specifically
interested in the microscopic distribution of benzo(a)pyrene
dioplexoide (PBDE), nitrosopyrene (NP), ethidium bromide (EB)
methylene blue (MB), copper ion (Cu+2), and singlet oxygen (*02)
attack sites within gene-sized DNA targets, and within the
nucleosome subunits of chromatin.  We have focused our attention
on two specific DNA regions as models for the coupling between
small molecule binding and local variation of DNA secondary
structure:  the oligo-A segments within kinetoplast DNA, and the
5' end of the human c-myc proto-oncogene.  For each, we have shown
that DNA structure is best described as a dynamic equilibrium, and
propose experiments to test the possibility that carcinogen binding
is allosterically coupled to the underlying equilibrium.  In a
related set of experiments, we have proposed to map the
distribution of BPDE and NP binding sites on the supF gene in the
mammalian shuttle vector pZ189.  It has been determined by others
that in a mammalian 293 cell line, BPDE-mediated mutagenesis in
supF is targeted to specific sequences.  The goal of this
subproject is to establish a rigorous relationship between
carcinogen binding and site specific mutagenesis in this mammalian
assay system.  The last major goal of this work is to explore the
sequence specific binding of single-strand oligonucleotide to the
c-myc gene control region.  We have shown that such interactions
occur, and result in the formation of a triple strand complex, by
a process which may be coupled to the DNA structure equilibrium
which we have detected in the myc control region.  We propose
experiments which will define the structure and specificity of this
complex, its coupling to DNA structure change, and its potential
as a repressor of myc gene expression.

## Key facts

- **NIH application ID:** 3178596
- **Project number:** 2R01CA039527-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** MICHAEL E. HOGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $210,167
- **Award type:** 2
- **Project period:** 1988-04-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178596

## Citation

> US National Institutes of Health, RePORTER application 3178596, MAPPING CARCINOGEN BINDING SITES ON GENES (2R01CA039527-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178596. Licensed CC0.

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