As guardians of the genome, RecQ helicases preserve our genetic coding and therefore protect our cells against aging. Likewise, Nuclear Pore Complexes (NPCs) maintain proper nuclear functionality through the transport of protein and mRNA. We hypothesize, from our preliminary work, that there exists a connection between RecQ helicases and specific proteins in the NPC that function together in maintenance of genomic longevity. Our goal is to gather quantitative data through targeted proteomics to prove this interdependence. Application of these methods will identify important RecQ helicases and Nups. We propose 1) to further test a panel of RecQ helicase knockout DT40 cells and mutant RecQ helicase fibroblasts for Nup protein and mRNA levels, 2) to analyze changes in nuclear transport by monitoring energy gradients and transport of NLS-GFP, 3) to obtain accurate measurements of NPC stoichiometry through targeted proteomics.

Public Health Relevance

Aging involves the buildup of harmful alterations in the cell over time. One factor in aging is genome instability, which results from a decreased accuracy during replication. These errors lead to acceleration of the process. In our proposal, we focus on DNA damage repair complexes that are associated with the Nuclear Pore Complex to conceivably bringing double strand breaks to the nuclear periphery for repair. Impairment of these connections may be a factor in enhanced aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG047433-01
Application #
8685574
Study Section
Special Emphasis Panel (ZRG1-SBIB-P (50))
Program Officer
Guo, Max
Project Start
2014-08-15
Project End
2016-07-31
Budget Start
2014-08-15
Budget End
2016-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$150,589
Indirect Cost
$50,589
Name
Stevens Institute of Technology
Department
Chemistry
Type
Schools of Engineering
DUNS #
064271570
City
Hoboken
State
NJ
Country
United States
Zip Code
07030