title: Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells.
abstract: OBJECTIVE
  Sublethal damage repair (SLDR) is a type of repair that occurs in split-dose irradiated cells, which was discovered more than 50 years ago. However, due to conflicting reported data, it remains unclear which DNA double-strand break (DSB) repair pathway, non-homologous end-joining (NHEJ) repair, homologous recombination repair (HRR) or both, contributes to SLDR, particularly in human cells. We were interested in clarifying this question.
  
  
  METHODS
  Mammalian cell lines, including human, mouse and Chinese hamster ovary (CHO) cell lines, wild type, deficient in NHEJ or HRR were irradiated with either single dose or two split doses at 2- or 4-h intervals. The clonogenic assay was used to evaluate these cell radiosensitivities.
  
  
  RESULTS
  All wild-type or HRR-deficient cells (including human, mouse and CHO cells) showed a higher survival rate after exposure to split-dose versus single-dose radiation; however, all classical NHEJ-deficient cells (including human, mouse and hamster cells) did not show any apparent sensitivity changes between single-dose and split-dose irradiation.
  
  
  CONCLUSIONS
  Classical NHEJ mainly contributes to SLDR in mammalian cells (including human cells). These results have the potential to improve radiotherapy.
authors.affiliation: Department of Radiation Oncology, the First Hospital, Jilin University, Changchun, 130021, China.|Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Solah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, the First Hospital, Jilin University, Changchun, 130021, China.|Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Bailong
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, the First Hospital, Jilin University, Changchun, 130021, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D003412:Cricetulus; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013045:Species Specificity
keywords: DNA DSB; DNA repair; HRR; NHEJ; SLDR; heavy ion