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Development of Fluorescent Probes for Sensing DNA Mismatches

Institution: California Institute of Technology
Investigator(s): Mi Hee Lim, Ph.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15FT-0166 Award: $65,369
Subject Area: General Biomedical Science
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
DNA damage induces human cancers. UV light or genotoxic chemicals cause DNA injury (base mismatches) contributing to genetic instability. Exposure to carcinogens in tobacco smoke is mostly responsible for cancers in human. Permanent DNA sequence changes (mutations) are a major source of cancers. Mismatch repair (MMR) machinery in biology repairs these DNA mismatches. If they are left without repair, they may increase the possibility and danger of cancers. Human hereditary nonpolyposis colon cancer and sporadic cancers are two examples produced by this. A tool for specific single base mismatch detection in DNA is required to monitor cancers in early stages, which may prevent diseases and help develop suitable diagnostics and chemotherapeutics. Fluorescent sensors provide a non-invasive and convenient means to visualize analytes in biological systems. A probe that consists of a fluorophore coupled to a base mismatch recognizing metal complexes will allow imaging of DNA mismatches in vivo.

DNA strand cleavage near a CC mismatch directed by a metalloinsertor
Periodical: Inorganic Chemistry Index Medicus:
Authors: Lim, M., Lau, I.H., Barton, J.K. ART
Yr: 2007 Vol: 46 Nbr: Abs: Pg: 9528-9530

Detection of a DNA lesion by Ru(bpy)2(DPPZ)2J
Periodical: Journal American Chemicaal Society Index Medicus:
Authors: Lim, M.H., Hang, S., Olmon, E.D. ART
Yr: 2008 Vol: Nbr: Abs: Pg:

Luminescent properties of RU(DPPZ) derivatives toward DNA defects
Periodical: Inorganic Chemistry Index Medicus:
Authors: Lim, M.H., Olmon, E.D., Hang, S., Dervan, E.E., Barton, J.K. ART
Yr: 2008 Vol: Nbr: Abs: Pg: