Repair of Clustered DNA Lesions in Double Strand Break Repair Deficient Human Tumor Cells

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Charles William Loftin (Creator)
Institution
East Carolina University (ECU )
Web Site: http://www.ecu.edu/lib/

Abstract: DNA-dependent protein kinase (DNA-PK) is a holoenzyme of three subunits, Ku70, Ku80, and the DNA-Pk catalytic subunit (DNA-PKcs). DNA-PK serves a role in non-homologous end joining to repair double stranded breaks, and has a suggested role in the expression of base excision repair (BER) proteins. Repair of DNA damage is vital to the prevention of malignant mutations. Oxidative induced clustered DNA lesions (OCDLs) is the occurrence of two or more closely located DNA lesions, and have been shown to be poorly repaired. DNA-PKcs is the phosphorylating unit of DNA-PK. DNA-PKcs deficient cells show increased radiosensitivity and decreased reparability. This study aimed to evaluate the role of DNA-PK in OCDL repair in DNA-PKcs deficient cells. This study showed decreased OCDL repair and a decreased expression of the BER protein XRCC1 in cells treated with DNA-PKcs specific inhibitors compared to non-treated cells. This study proposes that DNA-PK is involved in response to single and complex damage, and that inhibition of DNA-PKcs results in poor OCDL repair. Interest is growing in protein kinase inhibitors as supplemental aids to chemo and radiotherapies. This study and others indicates that DNA-PK is important to proficient DNA repair, indicating that DNA-PKcs inhibitors may have clinical relevance as supplemental aids to current cancer therapies in killing targeted cells.

Additional Information

Publication
Thesis
Language: English
Date: 2010
Keywords
Biology, General

This item references:

TitleLocation & LinkType of Relationship
Repair of Clustered DNA Lesions in Double Strand Break Repair Deficient Human Tumor Cellshttp://thescholarship.ecu.edu/bitstream/handle/10342/2727/Loftin_ecu_0600M_10130.pdfThe described resource references, cites, or otherwise points to the related resource.