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Full-Text Articles in Internal Medicine
Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao
Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao
ETSU Faculty Works
T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity …