# MOLECULAR GENETICS OF HSV DNA POLYMERASE GENE

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1989 · $169,916

## Abstract

The herpes simplex virus (HSV) DNA polymerase (pol) gene affords a unique
model system amenable to molecular, pharmacological, and genetic approaches
for studies of eukaryotic replicative polymerases.  The overall aim of
these studies is to understand the pol gene in detail in terms of its
structure, expression and function.

The availability of the DNA sequence of the pol gene permits the precise
location of its RNA transcripts by S-1 nuclease and exonuclease VII
mapping.  The gene can now be cloned as a single stretch of DNA permitting
its overexpression.  This will facilitate isolation of antibodies to
identify pol polypeptides in infected cells and to map them precisely onto
the pol gene.  The sequence predicts a number of features which may act to
diminish pol expression.  The role of these sequences and their importance
to the virus will be assessed by mutational analysis; they may reflect
general properties of polymerase genes.

Polymerase function will be explored by mapping and sequencing mutations
which differentially affect the deoxynucleoside triphosphate and
pyrophosphate binding sites.  These mutations cluster to define a substrate
binding domain.  Portions of the polymerase important for polymerase
function will also be identified by complementation experiments with
polymerases from HSV's relatives, Epstein-Barr virus and cytomegalovirus
(CMV).  Functional sites in the CMV pol gene will be identified by mutant
isolation and mapping studies.  Functional interactions of HSV polymerase
with other HSV proteins will be investigated through mapping of altered
drug sensitivity mutations to other loci and by mapping and sequencing
regions of polymerase involved in such interactions.  These studies of
polymerase function will be related to studies of polymerase structure and
its interaction with DNA using polymerase purified from an overexpression
system.

HSV and CMV are important human pathogens for which there are no known
cures.  Since HSV and CMV polymerase are targets for several licensed and
promising antiviral drugs, information from these studies should aid drug
development.  Similarly, HSV polymerase provides a model for human
Alpha-polymerase which is a potential target for antitumor drugs.  Studies
of drug resistance help elucidate drug mechanisms and predict properties of
drug resistant mutants in the clinic.  Thus, the proposed studies address
issues regarding eukaryotic DNA replication and issues of direct health
relevance.

## Key facts

- **NIH application ID:** 3129274
- **Project number:** 5R01AI019838-07
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** DONALD M COEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $169,916
- **Award type:** 5
- **Project period:** 1983-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129274

## Citation

> US National Institutes of Health, RePORTER application 3129274, MOLECULAR GENETICS OF HSV DNA POLYMERASE GENE (5R01AI019838-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3129274. Licensed CC0.

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