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Minimize RSR Award Detail

Research Spending & Results

Award Detail

Awardee:JOHNS HOPKINS UNIVERSITY, THE
Doing Business As Name:Johns Hopkins University
PD/PI:
  • Steven E Rokita
  • (410) 516-5793
  • rokita@jhu.edu
Award Date:06/13/2019
Estimated Total Award Amount: $ 375,000
Funds Obligated to Date: $ 375,000
  • FY 2019=$375,000
Start Date:08/01/2019
End Date:07/31/2022
Transaction Type:Grant
Agency:NSF
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.074
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:The Influence of Self-Repair on the Distribution of Cyclopyrimidine Dimers in DNA
Federal Award ID Number:1914560
DUNS ID:001910777
Parent DUNS ID:001910777
Program:Genetic Mechanisms
Program Officer:
  • Manju Hingorani
  • (703) 292-7323
  • mhingora@nsf.gov

Awardee Location

Street:1101 E 33rd St
City:Baltimore
State:MD
ZIP:21218-2686
County:Baltimore
Country:US
Awardee Cong. District:07

Primary Place of Performance

Organization Name:Johns Hopkins University
Street:1011 33rd St
City:Baltimore
State:MD
ZIP:21218-2686
County:Baltimore
Country:US
Cong. District:07

Abstract at Time of Award

The link between DNA damage caused by ultraviolet (UV) light and genetic mutation is well established, but the determinants of hotspots of photochemical reactivity where UV damage is most likely to occur remain elusive. This project will address the origins and locations of these hotspots with a focus on how damage accumulates as a result of competition between its formation and spontaneous self-repair. The outcomes should inform future strategies for better protection of genomes from UV damage. The project will offer cross-disciplinary training opportunities for graduate and undergraduate students as they study molecular processes affecting the viability of life under UV exposure, and prepare them for diverse careers that serve the public interest. Curvature of duplex DNA was previously reported as a crucial variable in the formation and distribution of photochemical damage. Whether this property controls initial formation of the products or their steady state levels, established by competing formation and self-repair processes, has yet to be determined. Similarly, the sequences of DNA where damage is most sensitive to curvature have not been determined. Both of these unknowns will be addressed by probing a library of DNA sequences that can be switched between linear and bent conformations. The reversibility of UV damage will be assessed by the rate at which product profiles created by these two states of DNA interconvert, and sequences within the library most influenced by bending will be characterized by deep sequencing. The sequences most susceptible to UV damage will be reconstructed by statistical analysis and used to validate the correlation between sequence, conformation and hyperreactivity in vitro. This award was co-funded by the Division of Molecular and Cellular Biosciences and the Division of Chemistry. 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.

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