Werner complex deficiency in cells disrupts the Nuclear Pore Complex and the distribution of lamin B1.

[werner syndrome]

From the surrounding shell to the inner machinery , nuclear proteins provide the functional plasticity of the nucleus . This study highlights the nuclear association of Pore membrane (POM ) protein NDC 1 and Werner protein (WRN ), a RecQ helicase responsible for the DNA instability progeria disorder , Werner Syndrome . In our previous publication , we connected the DNA damage sensor Werner 's Helicase Interacting Protein (WHIP ), a binding partner of WRN , to the NPC . Here , we confirm the association of the WRN /WHIP complex and NDC 1 . In established WRN /WHIP knockout cell lines , we further demonstrate the interdependence of WRN /WHIP and Nucleoporins (Nups ). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE ) but do affect the distribution of FG Nups and the RAN gradient , which are necessary for nuclear transport . Evidence from WRN /WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B 1 . The appearance of "RAN holes " void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B 1 . From WRN /WHIP knockout cell line extracts , we found three forms of lamin B 1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein . Upon treatment with topoisomerase inhibitors lamin B 1 cleavage occurs only in WRN /WHIP knockout cells . Our data suggest the link of the NDC 1 and WRN as one facet of the network between the nuclear periphery and genome stability . Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus .

Diseases
Validation

Diseases presenting "functional plasticity of the nucleus" symptom

werner syndrome

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