# OXIDATIVE DNA DAMAGE: REPAIR AND CELLULAR RESPONSES

> **NIH NIH R01** · HARVARD UNIVERSITY · 1991 · $153,675

## Abstract

Oxygen radicals are responsible for a large fraction of the toxic
and mutagenic effects of ionizing radiation.  Such radicals are
also produced by a variety of environmental chemicals and as side
products of normal aerobic metabolism.  Multilayered cellular
defenses have evolved in response to this threat, consisting in
part of some enzymes that prevent damage by scavenging reactive
oxygen species and others that repair free radical damage to the
critical molecular DNA.  These defenses are coordinated as
inducible systems in Escherichia coli that respond to different
kinds of oxidative stress.  One group of proteins (the soxR
regulon) is induced specifically by the intracellular generation
of superoxide radical and increases the levels of several enzymes
that destroy superoxide, produce reducing equivalents in the form
of NADPH, and repair oxidative damage to DNA.  Another set of
responses is triggered by hydrogen peroxide, and includes inducible
enzymes that destroy organic or hydrogen peroxides, along with a
large number of unknown inducible functions.  We will dissect the
biological functions of these adaptive responses to oxidative
stress by a detailed characterization of the soxR gene and its
regulon, and by the identification of H2O2-inducible  genes through
the use of gene fusions.  We will determine the DNA damages formed
in vivo that require the soxR-controlled enzyme endonuclease IV for
their repair.  This integrated molecular genetic and biochemical
analysis of the biological responses to oxidative damage in a
facile bacterial system will provide important information about
general biological mechanisms for dealing with the toxicity of
intrinsic and radiation-induced oxygen radical damage.

## Key facts

- **NIH application ID:** 3175696
- **Project number:** 5R01CA037831-07
- **Recipient organization:** HARVARD UNIVERSITY
- **SAM.gov UEI:** LN53LCFJFL45
- **Principal Investigator:** Bruce F. Demple
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $153,675
- **Award type:** 5
- **Project period:** 1984-08-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175696

## Citation

> US National Institutes of Health, RePORTER application 3175696, OXIDATIVE DNA DAMAGE: REPAIR AND CELLULAR RESPONSES (5R01CA037831-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175696. Licensed CC0.

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