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


ABSTRACT: Cardiovascular disease (CVD) is associated with both genetic variants and environmental factors. One unifying consequence of the molecular risk factors in CVD is DNA damage, which must be repaired by DNA damage response proteins. However, the impact of DNA damage on global cardiomyocyte protein abundance, and its relationship to CVD risk remains unclear. We therefore treated induced pluripotent stem cell-derived cardiomyocytes with the DNA-damaging agent Doxorubicin (DOX) and a vehicle control, and identified 4,178 proteins that contribute to a network comprising 12 co-expressed modules and 403 hub proteins with high intramodular connectivity. Five modules correlate with DOX and represent distinct biological processes including RNA processing, chromatin regulation and metabolism. DOX-corre

SUBMITTER: Johnson OD 

PROVIDER: S-EPMC11343126 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature