# Protein-nucleic acid interactions in basic cellular processes

> **NIH NIH R35** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $464,750

## Abstract

Abstract
Protein-nucleic acid interactions are central to many biological processes. Our research is
focused on two areas of protein-nucleic acid interactions: bacterial defense systems and
translesion DNA synthesis (TLS). The studies on bacterial defense systems are an extension of
our decades-long work on restriction-modification (R-M) systems. Over the past few years, many
new bacterial defense systems have been discovered, and motivated by our success with R-M
systems, we will undertake studies on two new systems: the cyclic oligonucleotide based anti-
phage signaling system (CBASS) and a short prokaryotic Argonaute (pAgo) system. We will
determine how these systems confer bacterial immunity; in particular, how they become
allosterically activated for abortive infection - to prevent propagation of the invading DNA
throughout the bacterial cell population. The studies on TLS are a continuation of our pioneering
work on TLS polymerases and in understanding how cells cope with DNA damage. Recent
advances in cryo-EM have allowed us to approach what seemed impossible at one-time, namely
the structure of the complex multi-subunit TLS polymerase Polz. Polz stands out as the pivotal
DNA polymerase in eukaryotes for maintaining genome integrity, and we will address how Polz
works in conjunction with another polymerase Rev1 to extend DNA synthesis from DNA lesions.
Together, these studies will set new paradigms in our understanding of bacterial immunity and in
how eukaryotic cells cope with daily genotoxic stresses.

## Key facts

- **NIH application ID:** 10841869
- **Project number:** 2R35GM131780-06
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ANEEL K. AGGARWAL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $464,750
- **Award type:** 2
- **Project period:** 2019-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841869

## Citation

> US National Institutes of Health, RePORTER application 10841869, Protein-nucleic acid interactions in basic cellular processes (2R35GM131780-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841869. Licensed CC0.

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