title: Downregulation of a novel human gene, ROGDI, increases radiosensitivity in cervical cancer cells.
abstract: ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation. Inhibition of cyclin-dependent kinases (CDKs) can lead to a halt of cell cycle progression and a stay at different phases or checkpoints. Our data show that the downregulation of ROGDI led to a decreased expression of CDK 1, 2, cyclin A, B and resulted in a G2/M phase transition block. In addition, the downregulation of ROGDI increased cell accumulation at the G2 phase as detected using flow cytometry and decreased cell survival as revealed by clonogenic assay in HeLa and C33A cells following irradiation. These findings suggest that the downregulation of ROGDI can mediate radiosensitivity by blocking cells at G2/M, the most radiosensitive phase of the cell cycle, as well as exerting deleterious effects in the form of DNA damage, as shown by increased γ-H2AX activation.
authors.affiliation: a Department of Biological Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chen
authors.affiliation: b Department of Medicine , College of Medicine, University of Florida , MSB, Gainesville , FL , USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Cho
authors.affiliation: c Division of Endocrinology & Metabolism , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Kaohsiung , Taiwan.
authors.forename: Tsai-Hua
authors.initials: TH
authors.lastname: Huang
authors.affiliation: a Department of Biological Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan.
authors.forename: Chao-Neng
authors.initials: CN
authors.lastname: Tseng
authors.affiliation: d Department of Radiation Oncology , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Kaohsiung , Taiwan.
authors.forename: Eng-Yen
authors.initials: EY
authors.lastname: Huang
authors.affiliation: a Department of Biological Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan.
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Cho
keywords: DNA; ROGDI; cyclin-dependent kinases; damage; radiosensitivity; γ-H2AX