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.
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: Sandra Segura-Bayona; Philip A Knobel; Helena González-Burón; Sameh A Youssef; Aida Peña-Blanco; Étienne Coyaud; Teresa López-Rovira; Katrin Rein; Lluís Palenzuela; Julien Colombelli; Stephen Forrow; Brian Raught; Anja Groth; Alain de Bruin; Travis H Stracker Journal: Cell Death Differ Date: 2017-07-14 Impact factor: 15.828
Authors: Vibha Singh; Praveen Kumar Jaiswal; Ishita Ghosh; Hari K Koul; Xiuping Yu; Arrigo De Benedetti Journal: Int J Cancer Date: 2019-02-25 Impact factor: 7.396