title: The expression of Tousled kinases in CaP cell lines and its relation to radiation response and DSB repair.
abstract: BACKGROUND
  The Tousled-like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLK1/1B interacts specifically with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, and with Rad9, a protein involved in DNA repair, and these interactions are believed to be responsible for the action of TLKs in double-strand break repair and radioprotection.
  
  
  METHODS
  Western blotting and RT-PCR were used to analyze the expression of TLK1, TLK1B, and TLK2 in a panel of prostate cancer (CaP) cell lines. The pattern of radiotolerance in the cell lines was analyzed in parallel. DU145 and PC-3 cells were also probed with assays utilizing transfected plasmids that could be cleaved in vivo with adeno-expressed HO nuclease to assess the potential contribution of TLK1/1B in DSB repair.
  
  
  RESULTS
  This is the first report of TLKs' expression in a panel of CaP cell lines and their relationship to radioresistance. Furthermore, expression of TLK1B in non-expressing PC-3 cells rendered them highly resistant to radiation, and conversely, knockdown to TLK1/1B in expressing DU145 reduced their radiotolerance.
  
  
  CONCLUSIONS
  TLKs appear to be intimately linked to the pattern of resistance to DNA damage, and specifically DSBs, a finding that was not reported before for any cell lines, and certainly not systematically for human prostate cell lines.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ronald
authors.forename: Gulshan
authors.initials: G
authors.lastname: Sunavala-Dossabhoy
authors.forename: Lisa
authors.initials: L
authors.lastname: Adams
authors.forename: Briana
authors.initials: B
authors.lastname: Williams
authors.forename: Arrigo
authors.initials: A
authors.lastname: De Benedetti
mesh_terms: D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy*; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011836:Radiation Tolerance
chemical_list: D011494:Protein Kinases; C121377:protein kinase U; D017346:Protein Serine-Threonine Kinases; C425323:TLK1 protein, human