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bioRxiv · 10.1101/2023.03.09.529154

DEK oncoprotein participates in heterochromatin replication via SUMO-dependent nuclear bodies

Pierzynska-Mach, A.·Czada, C.·Vogel, C.·Gwosch, E.·Osswald, X.·Bartoschek, D.·Diaspro, A.·Kappes, F.·Ferrando-May, E.
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Abstract

The correct inheritance of chromatin structure is key for maintaining genome function and preventing cellular transformation. DEK, a conserved chromatin protein, has recognized tumor-promoting properties, its overexpression being associated with poor prognosis in various cancer types. At the cellular level, DEK displays pleiotropic functions, influencing differentiation, apoptosis, and stemness, but a characteristic oncogenic mechanism remains elusive. Here, we report the identification of DEK bodies, focal assemblies of DEK occurring at specific, yet unidentified sites of heterochromatin replication. In these bodies, DEK localizes in direct proximity to active replisomes suggesting a function in the early maturation of heterochromatin. A high-throughput siRNA screen identifies SUMO as a major regulator of DEK body formation, linking DEK to the SUMO network that controls chromatin states and cell fate. This work combines and refines our previous data on DEK as a factor essential for heterochromatin integrity and facilitating replication under stress and delineates an avenue of further study for unraveling DEKs contribution to cancer development.

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Pierzynska-Mach, A., Czada, C., Vogel, C., Gwosch, E., Osswald, X., Bartoschek, D., Diaspro, A., Kappes, F., Ferrando-May, E.. 2023-03-10. DEK oncoprotein participates in heterochromatin replication via SUMO-dependent nuclear bodies. https://doi.org/10.1101/2023.03.09.529154

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