Is There a Synthetic Lethality Between FANCM-U and SMARCAL1 ?
ACOG ePoster. Sabet L. Apr 27, 2018; 211769
Liliya Sabet
Liliya Sabet
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Introduction: Our oncology lab recent results showed that there is a strong synthetic lethal interaction between BRCA1 and FANCM. We observed a similar synthetic lethal interaction between BLM, a DNA helicase, and FANCM, albeit somewhat weaker than that of BRCA1 and FANCM. Furthermore we showed that BRCA1 recruits BLM to the replication stress sites induced by the depletion of FANCM. Our data suggest that a FANCM inhibitor may be used to potentially kill cancers with BRCA1 mutations. Most recently another DNA helicase, SMARCAL1, was shown to resolve replication stress.

Methods: We proposed to test whether there is a synthetic lethal interaction between SMARCAL1 and FANCM-U by performing a Crystal Violet Cell Viability Assay. We transfected U2-OS, a human osteosarcoma cell line, with siRNA targeting Luciferase (serves as the negative control siRNA), FANCM-U, SMARCAL1, and both FANCM-U and SMARCAL1. Then we seeded 4,000 cells per well on a 12-well plate. 7 to 10 days later we stained the cells with Crystal Violet, a blue dye, to visualize viable cells. Finally we quantitated the amount of viable cells with a spectrometer. We repeated the Crystal Violet Cell Viability Assay three times to obtain a reproducible result.

Results: Based on spectrometer results the amount of viable cells or intensity of light detected in the control and FANCM-U and SMARCAL1 wells were similar.

Conclusion/Implications: This study did not show synthetic lethal interaction between FANCM-U and SMARCAL1. Further research is ongoing to support or oppose our hypothesis.

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