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Significance The RAD51 paralog RAD51C is among the homologous recombination (HR) genes known to be tumor suppressors. As with many tumor suppressors, a large number of variants of unknown significance… Click to show full abstract
Significance The RAD51 paralog RAD51C is among the homologous recombination (HR) genes known to be tumor suppressors. As with many tumor suppressors, a large number of variants of unknown significance have been identified, impairing informed genetic counseling and treatment of cancer patients. Providing a framework for variant classification, functional analyses of RAD51C variants identify variants that confer HR deficiency and sensitize to therapeutics, including a cluster in a conserved motif. Conversely, these functional analyses support structural predictions of RAD51 paralog complexes, BDCX2 and CX3. Thus, our molecular and biochemical analyses of RAD51C variants provide insight into the functioning of the RAD51 paralog complexes.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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