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Cancer cells subvert the primate-specific KRAB zinc finger protein ZNF93 to control APOBEC3B
Romain Forey1, Charlène Raclot1, Cyril Pulver1,2
1School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Abstract:
ZNF93 is a primate-restricted Krüppel-associated box zinc finger protein responsible for repressing 20- to 12-My-old L1 transposable elements. Here, we reveal that ZNF93 also regulates the key cancer driver APOBEC3B-a mutagenic enzyme linked to tumorigenesis and cancer progression. ZNF93 depletion impairs DNA synthesis, activates replication and DNA damage checkpoints, and triggers proinflammatory phenotypes. Conversely, its overexpression enhances resistance to exogenous genotoxic stress, mirroring the effects observed with APOBEC3B depletion. ZNF93 expression correlates with cell proliferation rates and is overexpressed in many cancer types. These findings suggest that ZNF93 serves as a critical guardian of genome integrity, co-opted by cancer cells to counterbalance APOBEC3B-induced and L1-derived genomic instability and inflammation.
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