# DNA Sensing and Signaling

> **NIH NIH R35** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $603,026

## Abstract

Summary
This research program stems from our past fundamental studies of DNA charge transport (DNA CT)
chemistry. This chemistry facilitates redox chemistry at a distance through the DNA duplex and
sensitively depends upon the integrity of the intervening base pair stack. Our goal now is to apply this
chemistry for the sensitive sensing of DNA lesions and DNA processing events electrically and,
importantly, to determine general characteristics of how DNA CT chemistry is utilized within the cell
for long range chemical signaling. In particular, these studies may establish a new framework for
considering the role of [4Fe4S] clusters in critically important enzymes that process DNA. With respect
to sensing, we will continue in the development and application of our multiplexed platform in
developing new electrochemical strategies for the detection of DNA-binding proteins and nucleic acid
markers associated with cancer. In general, our multiplexed DNA electrochemical platform offers a
completely new approach to sensitive, well-controlled detection of DNA-binding events. Our overall
goal is the development of highly sensitive sensors based on DNA CT chemistry that can be used to
monitor biomolecules in a single cell. Significantly, our goal also is to understand how Nature may use
DNA CT; we will continue our studies to characterize the redox chemistry of critically important DNA-
processing enzymes involved in replication and DNA repair to determine how this chemistry may be
utilized for long range signaling across the genome. We will use DNA electrochemistry anaerobically
using multiplexed DNA chips to characterize DNA-processing proteins containing redox-active [4Fe4S]
cofactors. Overall, experiments we have carried out thus far provide support that DNA CT signaling is a
means for diverse proteins with different roles in DNA processing to coordinate their activities as a
team. DNA CT may be used for polymerase hand-offs and to coordinate a rapid response to oxidative
stress. We will build upon this foundation by exploring DNA CT signaling among protein teams
involved in DNA transcription and replication as well as repair, using AFM assays, genetics, and
spectroscopy on [4Fe4S] proteins and mutants. We aim to use our expertise in the electrochemical and
biochemical characterization of DNA CT proficiency to identify new CT-active protein players and
illuminate the DNA CT signaling networks in which they participate. This work will contribute both to
our fundamental understanding of protein/DNA signaling and the important consideration of DNA CT
deficiencies associated with disease.

## Key facts

- **NIH application ID:** 10113640
- **Project number:** 5R35GM126904-04
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JACQUELINE K BARTON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $603,026
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113640

## Citation

> US National Institutes of Health, RePORTER application 10113640, DNA Sensing and Signaling (5R35GM126904-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10113640. Licensed CC0.

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