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8.27.2018

Sylvester Researchers Discover A Novel Mediator of Genome Instability Relevant to Many Cancers

A research team at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine has discovered a novel role for a protein factor that allows it to contribute to the genome instability observed in many cancer cells.

The investigators found that the FANCA protein plays an unexpected role in an error-prone DNA repair pathway that can drive the common instability mechanism.

“This discovery helps us understand a source and mechanism of genome instability, which is observed in roughly 90 percent of all human cancers,” said the study’s principal investigator Yanbin Zhang, Ph.D., a Sylvester member and associate professor of biochemistry and molecular biology. “More importantly, it opens up the possibility of treating cancers by targeting FANCA to reduce genome instability. Our recent data suggests that the amount of FANCA protein in cells correlates to breast cancer patient survival, and that targeting FANCA with certain chemical compounds may be able to kill cancer cells.”

The findings were published on August 16 as “FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange,” the cover story in the journal Molecular Cell. Dr. Zhang was the corresponding author; Anaid Benitez, Ph.D., Wenjun Liu, Ph.D., and graduate student Anna Palovcak were co-first authors.

The researchers are now screening for small molecule compounds that can block FANCA from causing genome instability. They expect such a compound will be useful in treating a variety of cancers with high FANCA expression.

“Cancers can be eradicated when we have mastered the mechanisms of how a normal cell becomes cancerous,” said Dr. Zhang. “Understanding how genome instability drives cancer development will provide us with a paradigm-shifting strategy for killing cancer cells.”

Dr. Zhang’s work was supported by a Flight Attendant Medical Research Institute (FAMRI) grant and two grants from the National Institutes of Health.

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