# DNA REPLICATION AFTER INSULT WITH UV

> **NIH NIH R01** · NORTHERN ILLINOIS UNIVERSITY · 1989 · $103,654

## Abstract

The project's long-term objectives are to help elucidate the
molecular processes involved in carcinogenesis and mutagenesis.
Specific aims relate to how the DNA lesions are handled in
various eukaryotic cells.  From studies with ultraviolet (UV)
radiation, ionizing radiation, and other mutagens/carcinogens it is
clear that DNA is the critical target for physical and chemical
carcinogens and mutagens.  The mere existence of lesions in DNA
may not, however, be sufficient to produce mutagenesis,
carcinogenesis or cell killing, since generally some type of
processing is required for such lesions to be "fixed" and thus result
in mutagenesis, carcinogenesis or cell killing.  This project
examines this processing by examining DNA replication after
insult of eukaryotic cells with UV (254 or 320 nm) light as well as
some other mutagens/carcinogens.  DNA replication was chosen
since existing data indicate that it plays a crucial role in the
processing of DNA lesions.  There are three general areas to be
explored.  First, our previous work has shown that exposure of
mammalian cells to UV light results in the activation of
alternative sites of replicon initiation.  Such an activation would
allow cells to replicate DNA that would normally be prevented
from being replicated by the presence of blocking lesions.  This
would increase cell survival, but might also increase the incidence
of mutagenesis or carcinogenesis since this process does not
remove lesions, but does stimulate cells to replicate regions of
DNA with non-instructive bases.  By using DNA fiber
autoradiography we plan to continue our work in this area and to
expand our study to other cells lines.  Second, using DNA fiber
autoradiography, we plan to continue our examination of the
effects of UV light and the rate and extent of DNA fork
progression.  From such studies we hope to be able to identify the
lesion(s) most responsible for blocking DNA fork progression.
Finally, exposure to UV appears to inhibit the activation of some
replicon clusters.  This process appears to occur for a longer time
(after exposure to UV) than does blockage to DNA fork
progression.  Using alkaline step elution, we plan to examine this
process in detail.  Examination of these three areas should
increase our understanding of how cells handle potentially
mutagenic/carcinogenic lesions.  This, in turn, should increase our
understanding of the molecular processes involved in mutagenesis
and carcinogenesis.

## Key facts

- **NIH application ID:** 3170472
- **Project number:** 5R01CA032579-08
- **Recipient organization:** NORTHERN ILLINOIS UNIVERSITY
- **SAM.gov UEI:** M2EEE68GGCY9
- **Principal Investigator:** THOMAS DANIEL GRIFFITHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $103,654
- **Award type:** 5
- **Project period:** 1982-03-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170472

## Citation

> US National Institutes of Health, RePORTER application 3170472, DNA REPLICATION AFTER INSULT WITH UV (5R01CA032579-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170472. Licensed CC0.

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