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PKCδ regulates chromatin remodeling and DNA repair through SIRT6 by Trisiani Affandi; Ami Haas; Angela M. Ohm; Gregory M. Wright; Joshua C. Black; Mary E. Reyland is a scholarly article available to read on EtoBox.

What is PKCδ regulates chromatin remodeling and DNA repair through SIRT6 about?

Protein kinase C delta (PKCδ) is a ubiquitous kinase whose function is defined in part by localization to specific cellular compartments. Nuclear PKCδ is both necessary and sufficient for IR-induced apoptosis, while inhibition of PKCδ activity provides radioprotection __in vivo.__ How nuclear PKCδ regulates DNA-damage induced cell death is poorly understood. Here we show that PKCδ regulates histone modification, chromatin accessibility, and double stranded break (DSB) repair through a mechanism that requires SIRT6. Overexpression of PKCδ promotes genomic instability and increases DNA damage and apoptosis. Conversely, depletion of PKCδ increases DNA repair via non-homologous end joining (NHEJ) and homologous recombination (HR) as evidenced by more rapid formation of NHEJ (DNA-PK) and HR (Rad51) DNA damage foci, increased expression of repair proteins, and increased repair of NHEJ and HR fluorescent reporter constructs. Nuclease sensitivity indicates that PKCδ depletion is associated with more open chromatin, while overexpression of PKCδ reduces chromatin accessibility. Epiproteome analysis revealed that PKCδ depletion increases chromatin associated H3K36me2, and reduces ribosylation

Author

Trisiani Affandi; Ami Haas; Angela M. Ohm; Gregory M. Wright; Joshua C. Black; Mary E. Reyland

Publisher

Cold Spring Harbor Laboratory

Published

2023

Language

EN