PLK1 Phosphorylates WRN at Replication Forks DOI
Lei Wang, Daheng He,

Qianjin Li

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 392(2), P. 100051 - 100051

Published: Nov. 30, 2024

Prostate cancer, particularly castration-resistant prostate remains a serious public health issue. Androgen signaling inhibitors have emerged as major treatment approach but with limited success. Thus, identification of novel targets is high clinical relevance. Polo-like kinase 1 (PLK1) has documented roles in various aspects including resistance to androgen inhibitors. Radiotherapy another for treating how Plk1 might regulate the efficacy radiotherapy unknown. Nonhomologous end joining (NHEJ) and homologous recombination (HR) are 2 DNA repair pathways, cellular choices between NHEJ HR being elegantly regulated by end-processing. However, long-range resection poorly understood. It been that Werner syndrome protein (WRN) actively involved pathway. In this study, we demonstrate PLK1-associated phosphorylation WRN regulates at double-strand breaks, thereby promoting chromosome stability. Cells expressing nonphosphorylatable mutant show phenotype similar null cells because they lack ability increase NHEJ. summary, reveal Mre11, Rad50 Nbs1 promotes resection, eventually affecting break pathways. SIGNIFICANCE STATEMENT: Both damage PLK1 play critical cancer. The data presented here will provide guidance on manipulate improve settings.

Language: Английский

PLK1 Phosphorylates WRN at Replication Forks DOI
Lei Wang, Daheng He,

Qianjin Li

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 392(2), P. 100051 - 100051

Published: Nov. 30, 2024

Prostate cancer, particularly castration-resistant prostate remains a serious public health issue. Androgen signaling inhibitors have emerged as major treatment approach but with limited success. Thus, identification of novel targets is high clinical relevance. Polo-like kinase 1 (PLK1) has documented roles in various aspects including resistance to androgen inhibitors. Radiotherapy another for treating how Plk1 might regulate the efficacy radiotherapy unknown. Nonhomologous end joining (NHEJ) and homologous recombination (HR) are 2 DNA repair pathways, cellular choices between NHEJ HR being elegantly regulated by end-processing. However, long-range resection poorly understood. It been that Werner syndrome protein (WRN) actively involved pathway. In this study, we demonstrate PLK1-associated phosphorylation WRN regulates at double-strand breaks, thereby promoting chromosome stability. Cells expressing nonphosphorylatable mutant show phenotype similar null cells because they lack ability increase NHEJ. summary, reveal Mre11, Rad50 Nbs1 promotes resection, eventually affecting break pathways. SIGNIFICANCE STATEMENT: Both damage PLK1 play critical cancer. The data presented here will provide guidance on manipulate improve settings.

Language: Английский

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