Cell cycle-dependent resolution of DNA double-strand breaks
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Susanna Ambrosio1, Giacomo Di Palo2, Giuliana Napolitano1, Stefano Amente2, Gaetano Ivan Dellino3,4, Mario Faretta3, Pier Giuseppe Pelicci3,4, Luigi Lania2, Barbara Majello1
1Department of Biology, University of Naples ‘Federico II’, Naples, Italy
2Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy
3Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
4Department of Oncology and Haemato-oncology, University of Milan, Italy
Luigi Lania, e-mail: firstname.lastname@example.org
Barbara Majello, e-mail: email@example.com
Keywords: cell-cycle, DSB repair, site-specific DSBs, AsiSI restriction enzyme
Received: November 05, 2015 Accepted: November 27, 2015 Published: December 17, 2015
DNA double strand breaks (DSBs) elicit prompt activation of DNA damage response (DDR), which arrests cell-cycle either in G1/S or G2/M in order to avoid entering S and M phase with damaged DNAs. Since mammalian tissues contain both proliferating and quiescent cells, there might be fundamental difference in DDR between proliferating and quiescent cells (or G0-arrested). To investigate these differences, we studied recruitment of DSB repair factors and resolution of DNA lesions induced at site-specific DSBs in asynchronously proliferating, G0-, or G1-arrested cells. Strikingly, DSBs occurring in G0 quiescent cells are not repaired and maintain a sustained activation of the p53-pathway. Conversely, re-entry into cell cycle of damaged G0-arrested cells, occurs with a delayed clearance of DNA repair factors initially recruited to DSBs, indicating an inefficient repair when compared to DSBs induced in asynchronously proliferating or G1-synchronized cells. Moreover, we found that initial recognition of DSBs and assembly of DSB factors is largely similar in asynchronously proliferating, G0-, or G1-synchronized cells. Our study thereby demonstrates that repair and resolution of DSBs is strongly dependent on the cell-cycle state.
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