Dr. Jac Nickoloff, Professor and Head of the Department of Environmental and Radiological Health Sciences, recently received a four-year, $1,176,000 grant from the National Institute of General Medical Sciences to study a novel human DNA repair protein called Metnase. The NIGMS is one of the National Institutes of Health.
The grant, which began in March 2009, will enable Dr. Nickoloff to continue studies on the Metnase protein. The protein regulates DNA repair of damage caused by radiation, chromosomal translocations, the DNA replication stress response, and chromosome decatenation (untangling) when cells divide. The protein also regulates cellular sensitivity to commonly used cancer drugs and may be an important biomarker that will allow physicians to customize therapies for more effective cancer treatments. These studies may lead to more efficient and safer human gene therapy protocols.
“This project will further clarify the protein interaction partners of Metnase and mechanisms underlying its roles in chromosomal translocations, DNA replication, and DNA repair,” said Dr. Nickoloff.
Metnase is a recently evolved human fusion protein that promotes random DNA integration and nonhomologous end-joining, and it stimulates chromosome decatenation by Topoisomerase IIα.
“We currently are testing whether manipulating Metnase levels or activity can be used to enhance homology-directed gene targeting in human cells,” said Dr. Nickoloff. “Metnase may also be an important factor in Topoisomerase IIα-mediated chromosome translocations that cause secondary tumors in patients treated with chemotherapeutics that inhibit Topoisomerase IIα.”
Dr. Nickoloff’s grant from the NIGMS reflects the institute’s mission to support research that increases understanding of life processes and lays the foundation for advances in disease diagnosis, treatment, and prevention.