Journal Article

DKFZ-2023-02496

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. (Last author)DKFZ*

2023
Company of Biologists Limited Cambridge

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Please use a persistent id in citations: doi:10.1242/jcs.261329

Abstract: The correct inheritance of chromatin structure is key for maintaining genome function and cell identity and preventing cellular transformation. DEK, a conserved non-histone 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 has remained elusive. Here we report the identification of DEK bodies, focal assemblies of DEK regularly occurring at specific, yet unidentified sites of heterochromatin replication exclusively in late S-phase. In these bodies, DEK localizes in direct proximity to active replisomes in agreement with a function in the early maturation of heterochromatin. A high-throughput siRNA screen, supported by mutational and biochemical analyses, identifies SUMO as one regulator of DEK body formation, linking DEK to the complex SUMO protein 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 DEK´s contribution to cancer development.

Keyword(s): Breast cancer ; Histone modification ; Oncogene ; Replication stress ; SiRNA screen ; Superresolution microscopy

Note: #LA:W650# / 2023 Dec 1;136(23):jcs261329

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Contributing Institute(s):

1. Enabling Technology (W650)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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