University of Louisville
Arsenic Exposure Induces Aneuploidy and Slows Growth in Yeast
Institution
University of Louisville
Faculty Advisor/ Mentor
J. Christopher States; Steven Ellis
Abstract
Arsenic, a poisonous metallic element, affects millions of people worldwide. The US EPA sets the MCL for arsenic at 10 ppb, yet countless individuals are exposed to drinking water levels well exceeding this safety standard. Chronic arsenic exposure has been shown to induce bladder, lung, liver and kidney cancer. Arsenic acts as a carcinogen by inducing aneuploidy in cells. It has been proposed that one manner in which arsenic induces aneuploidy is by inhibiting correct mitotic division in the spindle checkpoint. It is hypothesized that arsenic interferes with this checkpoint through interaction with APC11. APC11 is a zinc RING finger protein that acts as a catalyst subunit of the APC/C. Arsenic is believed to interact with APC11 by binding to two cysteine residues on the surface of the protein. These residues are important in the binding of a zinc atom in the zinc RING finger structure. In human cells, arsenic is known to slow growth and induce aneuploidy. Experimentation yielded identical results in the YNN541 yeast strain-a yeast strain used as a model to study aneuploidy. Thus, this strain can be used as a model system for human cells due to the similar effects produced by arsenic exposure.
Arsenic Exposure Induces Aneuploidy and Slows Growth in Yeast
Arsenic, a poisonous metallic element, affects millions of people worldwide. The US EPA sets the MCL for arsenic at 10 ppb, yet countless individuals are exposed to drinking water levels well exceeding this safety standard. Chronic arsenic exposure has been shown to induce bladder, lung, liver and kidney cancer. Arsenic acts as a carcinogen by inducing aneuploidy in cells. It has been proposed that one manner in which arsenic induces aneuploidy is by inhibiting correct mitotic division in the spindle checkpoint. It is hypothesized that arsenic interferes with this checkpoint through interaction with APC11. APC11 is a zinc RING finger protein that acts as a catalyst subunit of the APC/C. Arsenic is believed to interact with APC11 by binding to two cysteine residues on the surface of the protein. These residues are important in the binding of a zinc atom in the zinc RING finger structure. In human cells, arsenic is known to slow growth and induce aneuploidy. Experimentation yielded identical results in the YNN541 yeast strain-a yeast strain used as a model to study aneuploidy. Thus, this strain can be used as a model system for human cells due to the similar effects produced by arsenic exposure.