Related Experiment Video

Updated: Mar 12, 2026

Detection of Copy Number Alterations Using Single Cell Sequencing
09:45

Detection of Copy Number Alterations Using Single Cell Sequencing

Published on: February 17, 2017

12.2K

Detection of Nucleotide Disbalance in Cells Undergoing Oncogene-Induced Senescence

Mikhail A Nikiforov1, Donna S Shewach2

  • 1Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC L3-317, Elm & Carlton Streets, Buffalo, NY, 14263, USA. Mikhail.Nikiforov@Roswellpark.org.

Methods in Molecular Biology (Clifton, N.J.)
|November 5, 2016
PubMed

Insights

Oncogene-induced senescence involves DNA damage due to depleted deoxyribonucleotides. Measuring these nucleotide pools in senescent cells is crucial for understanding this process.

Area of Science:

  • Cellular senescence
  • DNA damage response
  • Oncogene signaling

Background:

  • Activated oncogenes trigger senescence phenotypes in normal human cells via DNA damage response.
  • Depletion of intracellular deoxyribonucleotide pools is a key cause of DNA damage during oncogene-induced senescence.
  • Decreased expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) contributes to deoxyribonucleotide pool depletion.

Purpose of the Study:

  • To describe a methodology for quantitatively measuring nucleotide pools in senescent cells.
  • To investigate the role of deoxyribonucleotide pool depletion in oncogene-induced senescence.

Main Methods:

  • Quantitative measurement of intracellular deoxyribonucleotide pools.
  • Analysis of thymidylate synthase (TS) and ribonucleotide reductase (RR) expression.
  • Induction of senescence using activated HRAS or C-MYC depletion.

Main Results:

  • Depletion of TS or RR individually induces premature senescence.
  • Ectopic expression of TS and RR suppresses senescence phenotypes.
  • Addition of deoxyribonucleosides also suppresses senescence phenotypes.

Conclusions:

  • Deoxyribonucleotide pool depletion is a critical mechanism driving oncogene-induced senescence.
  • Targeting nucleotide biosynthesis pathways may offer therapeutic strategies for senescence-related conditions.
  • Accurate measurement of nucleotide pools is essential for studying senescence.
Keywords:
C-MYCDNA damageRibonucleotide reductase (RR)Thymidylate synthase (TS)

More Related Videos

Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells08:56

Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells

Published on: July 12, 2022

3.6K
Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay10:32

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay

Published on: February 3, 2022

8.3K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.3K