Identification and Characterization of a Human MORC2 DNA Binding Region That is Required for Gene Silencing

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2024 Dec 31

PMID 39739841

Authors

Nikole L Fendler

Jimmy Ly

Luisa Welp

Dan Lu

Fabian Schulte

Henning Urlaub

Seychelle M Vos

Affiliations

Soon will be listed here.

Abstract

The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically. We identified a DNA binding site in the C-terminus of the protein, and we observe that this region can be phosphorylated in cells. DNA binding by MORC2 reduces its ATPase activity and MORC2 can entrap multiple DNA substrates between its N-terminal GHKL and C-terminal coiled coil 3 dimerization domains. Finally, we observe that the MORC2 C-terminal DNA binding region is required for gene silencing in cells. Together, our data provide a model to understand how MORC2 engages with DNA substrates to mediate gene silencing.

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