# Chromosomal death due to misincorporation of wrong material into DNA

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $307,302

## Abstract

Cancer and bacterial infections are caused by uncontrolled multiplication of undesired cell
types within the organism. Effective treatments target critical and specific parts of these
undesired cells, absent in by-stander cells of the organism. One successful strategy to fight
cancer or infections is to target the complex DNA metabolism of the undesired cells, causing
their chromosomal death, — a mysterious phenomenon, whose mechanisms are still
completely unclear. Chromosomal death is the inability to continue chromosome cycle —the
cycle of replication and segregation of genetic information that drives the cell cycle. The
chromosomal cycle is blocked by chromosomal lesions — DNA lesions that are so complex
and harmful, that they inactivate the entire chromosomes. A classic chromosomal lesion is a
double-strand DNA break, but the most common chromosomal lesions are efficiently mended
by pathways of recombinational repair and various back-ups. We are purposefully looking for
and characterizing conditions that induce irreparable chromosomal lesions that cause
chromosomal death, to make it possible to convert them into future treatments against
undesirable cells. This application describes our characterization of two such conditions: (i)
thymine starvation; (ii) toxic RNA incorporation into DNA. In characterizing a chromosome-
associated lethal phenomenon, we practice a three-pronged approach. On the one hand, we
identify the most dramatic physical readouts; on the other hand, we identify the most
interesting phenotypes of mutants. The third arm of the analysis is to look at the
chromosome from the genome perspective. Our fist specific aim will address genetic and
metabolic aspects of thymine starvation in relation to its three distinct phases. The second
specific aim will characterize physical changes in the chromosome during thymine starvation.
The third aim is about comprehensive characterization of the novel phenomenon of the
unexpected RNA nucleotide toxicity within the chromosomal DNA. Combining the most
relevant physical readouts with the most interesting mutants and the most dramatic
genomic patterns should yield a comprehensive 3D-picture of the phenomenon in genetic /
physical / genomic dimensions, producing mechanistic insights into the most complicated
mechanisms of chromosomal death.

## Key facts

- **NIH application ID:** 9841940
- **Project number:** 5R01GM073115-11
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Andrei Kuzminov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $307,302
- **Award type:** 5
- **Project period:** 2007-06-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841940

## Citation

> US National Institutes of Health, RePORTER application 9841940, Chromosomal death due to misincorporation of wrong material into DNA (5R01GM073115-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9841940. Licensed CC0.

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