# STRUCTURE & FUNCTIONAL ANALYSIS OF ADENOVIRUS GENOMES

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 1991 · $141,679

## Abstract

The overall objective of this proposal is to unravel the molecular
mechanism by which adenovirus DNA replicates in animal cells.
Adenovirus DNA replication system is an excellent model system
to understand how other viruses replicate in the infected host cell
and in addition, how DNA replication initiates in a eukaryotic
organism, in general.  Two viral coded gene products, the precusor
of terminal protein, which is covalently attached to the mature
viral DNA (pTP) and a DNA polymerase (Ad Pol) are the essential
components of viral DNA replication in vitro and in vivo.
Purification of the proteins from the adenovirus-infected HeLa
cells yielded a stable complex which is essential for initiation and
elongation of DNA replication.  A  transient expression system in
monkey cells, achieved by DNA-mediated transfection
methodology has provided preliminary evidence that 1) there is a
nuclear targeting signal domain in pTP, which targets this protein
to the nucleus of the transfected cells, and 2) both pTP and Ad
Pol interact, when their respective genes were co-transfected.  In
order to understand the molecular mechanisms of DNA
replication, it is important to identify the functional domains of
pTP and Ad Pol involved in this interaction.  A large number of
mutants will be isolated in the coding sequences of pTP and Ad
Pol by 1) linker-insertion/deletion 2) linker scanning 3) deletion
loop and 4) mixed oligonucleotide mutagenesis methods.  These
mutants will be assayed, using immunofluorescence microscopy,
immunoprecipitation techniques and by in vitro replication
reactions, to identify the signal domain of pTP involved in its
nuclear localization and the domains of pTP and Ad Pol involved
in interaction for their function in the initiation of DNA
replication.  The proposed model that the homologous adenovirus
DNA binding protein interacts with Ad Pol during DNA replication
will also be tested by using these methods.

## Key facts

- **NIH application ID:** 3171048
- **Project number:** 5R01CA033099-07
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **SAM.gov UEI:** YXJGGNC5J269
- **Principal Investigator:** Radhakrishnan Padmanabhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $141,679
- **Award type:** 5
- **Project period:** 1983-12-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171048

## Citation

> US National Institutes of Health, RePORTER application 3171048, STRUCTURE & FUNCTIONAL ANALYSIS OF ADENOVIRUS GENOMES (5R01CA033099-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3171048. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*