Excellence in Research: Investigation of RECQ1 helicase in DNA transactions upon oxidative stress

Howard University, Washington DC

Investigators

Abstract

The characteristics of each cell are defined by its DNA, a double-stranded helical molecule composed of two intertwined single strands of DNA. During the normal course of life cells sustain DNA damage, which must be repaired to maintain genetic integrity. This project will investigate how RECQ1, a DNA helicase that separates the two strands of DNA, helps repair DNA damage and maintain genome stability. RecQ helicases are present in all kingdoms of life and therefore this work will have broad relevance. This research will promote the careers of both graduate and undergraduate students. The work will provide opportunities to earn course credits for Directed Research or for an Honors thesis in the Department of Biochemistry and Molecular Biology at Howard University. Hands-on training in fundamental laboratory skills and interdisciplinary research training will prepare students for success in graduate education and in their future scientific careers in academia or in industrial biotechnology. The PI also performs outreach to broaden participation of women in science through the American Association of University Women, the NIH Women of Color in Science, and through another NSF initiative called HU-ADVANCE-IT. The central hypothesis of this project is that RECQ1 acts as a barrier against genetic instability triggered by oxidative stress and the functional association of RECQ1 with oxidatively damaged chromatin ensures faithful expression and propagation of genetic information. The first aim is to establish the role of RECQ1 in activation of DNA damage response to oxidative stress and in replication fork progression during repair of oxidative DNA damage. In the second aim, unbiased biochemical and cellular approaches will be employed to determine catalytic activities of RECQ1 and its interacting protein partners that allow it to facilitate repair of oxidative DNA damage. The final aim will test the impact of RECQ1 on transcriptional response to oxidative DNA damage and whether this is mediated through specific binding to genomic regions susceptible to oxidation or form G-quadruplexes. Collectively, this research will ascertain the exact role of RECQ1 helicase under oxidative stress at the levels of replication, repair and transcriptional control. This knowledge will also help determine whether different RecQ family members have functional redundancies or whether they have specialized functions that may be critical in regulating oxidative (and other genotoxic) stress in the cell. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.