title: Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin.
abstract: Cofilin is an actin-associated protein that belongs to the actin depolymerization factor/cofilin family and is important for regulation of actin dynamics. Cofilin can import actin monomers into the nucleus under certain stress conditions, however the biological effects of nuclear transport are unclear. In this study, we found that over-expression of cofilin led to increased radiation sensitivity in human non-small lung cancer H1299 cells. Cell survival as determined by colony forming assay showed that cells over-expressing cofilin were more sensitive to ionizing radiation (IR) than normal cells. To determine whether the DNA repair capacity was altered in cofilin over-expressing cells, comet assays were performed on irradiated cells. Repair of DNA damage caused by ionizing radiation was detected in cofilin over-expressing cells after 24 h of recovery. Consistent with this observation, the key components for repair of DNA double-strand breaks, including Rad51, Rad52, and Ku70/Ku80, were down-regulated in cofilin over-expressing cells after IR exposure. These findings suggest that cofilin can influence radiosensitivity by altering DNA repair capacity.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA. lee_yi_jang@hotmail.com
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
authors.forename: Tzong-Jen
authors.initials: TJ
authors.lastname: Sheu
authors.forename: Peter C
authors.initials: PC
authors.lastname: Keng
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D034961:Antigens, Nuclear / Q000096:biosynthesis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D020552:Comet Assay; D003285:Contractile Proteins / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D006801:Humans; D000072200:Ku Autoantigen; D008175:Lung Neoplasms / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry*; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D013997:Time Factors
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D034961:Antigens, Nuclear; D003285:Contractile Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen