# ENZYMOLOGY OF NORMAL AND VIRUS-INFECTED BACTERIA

> **NIH NIH R01** · OREGON STATE UNIVERSITY · 1987 · $160,316

## Abstract

This research uses T4 bacteriophage for explorations of relationships
between DNA precursor biosynthesis and DNA replication.  The intracellular
organization and control of the enzymes of deoxyribonucleoside triphosphate
(dNTP) production affects both rate and fidelity of DNA replication.  Since
many anticancer, antiviral, and antimicrobial drugs act via interference
with dNTP biosynthesis, further understanding of these relationships may
suggest more effective ways to use existing drugs.  T4 phage-infected
bacteria form a complex of viral and host enzymes of dNTP synthesis, which
seems to be juxtaposed with the replication apparatus and maintains local
DNA precursor concentrations at the high levels needed to sustain vigorous
DNA replication.

This research will continue to test the model described above.  This
involves investigations of the structure, activities, assembly, and
regulation of the isolated T4 dNTP-synthesizing complex, and purification
of most or all of the constituent enzymes in quantities sufficient for
attempted reconstitution studies and for analysis of protein-protein and
protein-nucleic acid interactions.  These experiments will involve affinity
chromatography using immobilized protein columns, fluorescence anisotropy
studies, and extension of experiments we have begun with protein
cross-linking agents.

Other projects will investigate parameters of dNTP biosynthesis and
compartmentation as possible determinants of the fidelity of DNA
replication.  This will involve in vivo studies, where genetic lesions
affecting DNA precursor synthesis are correlated with dNTP pool sizes and
both spontaneous and analog-induced mutation rates; and in vitro studies,
which determine the effects of high dNTP concentrations upon replication
error frequencies at defined loci.

Finally, investigations of gene organization and expression in the region
of the T4 genome between genes 63 and 32 will continue.  Sequence
determination of gene frd, which encodes dihydrofolate reductase (DHFR),
generated some surprises, including an overlap with the downstream td gene,
which encodes thymidylate synthase, and an upstream open reading frame
which in some respects looks like a DHFR pseudogene.  The biological
significance of these features will be studied.

## Key facts

- **NIH application ID:** 3126043
- **Project number:** 5R01AI015145-11
- **Recipient organization:** OREGON STATE UNIVERSITY
- **SAM.gov UEI:** MZ4DYXE1SL98
- **Principal Investigator:** CHRISTOPHER K MATHEWS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $160,316
- **Award type:** 5
- **Project period:** 1978-01-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126043

## Citation

> US National Institutes of Health, RePORTER application 3126043, ENZYMOLOGY OF NORMAL AND VIRUS-INFECTED BACTERIA (5R01AI015145-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126043. Licensed CC0.

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