ICE Bioscience Posters

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WRN is a nuclear protein with two known enzymatic functions: a 3'-5' exonuclease activity residing in the amino-terminal region and ATP-dependent 3'-5' DNA helicase unwinding activity, which has roles in various cellular processes that are crucial for the maintenance of genome stability.

Cancers with microsatellite instability (MSI) result from mutations in mismatch repair genes, leading to broadly distributed insertions and/or deletions of TA-dinucleotide repeats within microsatellite regions across the genome.

WRN is required for unwinding problematic DNA structures found in MSI-H cells, and the loss of WRN during cell replication leads to dsDNA breaks and the initiation of a DNA repair response. WRN emerges as a promising synthetic lethal target in MSI-H cancers.