Related Experiment Video

Updated: Mar 7, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
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Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

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DNA-damage-associated protein co-expression network in cardiomyocytes informs on tolerance to genetic variation and

Omar Darrel Johnson1,2, Sayan Paul3, José Angel Gutiérrez3

  • 1Biochemistry, Cellular and Molecular Biology Graduate Program, University of Texas Medical Branch, Galveston, TX 77555, USA.

Iscience
|June 5, 2025
PubMed

Insights

DNA damage from cardiovascular disease risk factors impacts heart cell proteins. This study reveals how DNA damage affects protein networks and influences genetic variation tolerance, offering insights into heart disease mechanisms.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Cardiovascular disease (CVD) arises from genetic and environmental factors, often leading to DNA damage.
  • DNA damage is a consequence of multiple CVD risk factors.
  • Understanding the cardiomyocyte proteome's response to DNA damage is crucial for CVD research.

Purpose of the Study:

  • To investigate how DNA damage influences the cardiomyocyte proteome.
  • To explore the relationship between DNA damage-induced proteomic changes and CVD risk.
  • To analyze protein network dynamics in response to DNA damage.

Main Methods:

  • Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes were treated with doxorubicin (DOX), a DNA-damaging agent.
  • A protein-protein interaction network was constructed from 4,178 proteins.
  • Co-expressed modules and hub proteins associated with DOX treatment were identified and analyzed.

Main Results:

  • Twelve co-expressed modules and 403 hub proteins were identified. Five modules correlated with DOX treatment and were linked to RNA processing, chromatin regulation, and metabolism.
  • DOX-correlated hub proteins showed reduced variation due to genetic factors but were enriched in loss-of-function intolerant genes.
  • These proteins were enriched for physical interactors of known CVD risk proteins, though not for known CVD risk proteins themselves.

Conclusions:

  • Protein connectivity within DNA-damage-associated modules affects tolerance to genetic variation.
  • Dynamic network analysis can reveal insights into complex traits like cardiovascular disease.
  • The findings highlight the intricate interplay between DNA damage, proteomic networks, and genetic susceptibility in CVD.
Keywords:
Integrative aspects of cell biologyMolecular networkProteomics

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