Masking DNA Single-Strand Break (SSB): a New Approach to Cancer Treatment

by Shu Zhang

Institution: Wesleyan University
Department: Chemistry
Year: 2014
Keywords: DNA damage; DNA damage repair; Synthetic Lethality; SSB; DSB
Record ID: 2034993
Full text PDF: http://wesscholar.wesleyan.edu/etd_mas_theses/78


Certain types of cancer have defective repair mechanisms, which can cause the accumulation of damaged DNA. The persistent DNA damage can stall replication process and cause cell death. This type of defect found in cancer cells allows the development of new cancer treatment by exploiting the weakness of repair pathways. One alternative approach is to hide the damaged DNA from the malfunction repair mechanism. The aim of the research is to discover drug-like molecules that could mask the damaged site on duplex DNA. Spermine, spermidine, tetralysine, hoechest33258, DAPI, netropsin, berenil, and ethidium bromide (EtBr) have been tested for this purpose. An improved hydroxyl radical cleavage protocol is used to cleave the DNA to obtain structural information of the damaged site in the presence and absence of ligand. The preliminary result indicates that EtBr discriminates the damaged site on DNA. Other ligands fail to produce binding specificity relative to the damaged site.