Cell cycle-dependent resolution of DNA double-strand breaks

Susanna Ambrosio, Giacomo Di Palo, Giuliana Napolitano, Stefano Amente, Gaetano Ivan Dellino, Mario Faretta, Pier Giuseppe Pelicci, Luigi Lania, Barbara Majello

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)4949-4960
Number of pages12
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 2016

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Keywords

  • AsiSI restriction enzyme
  • Cell-cycle
  • DSB repair
  • Site-specific DSBs

ASJC Scopus subject areas

  • Oncology

Cite this

Ambrosio, S., Di Palo, G., Napolitano, G., Amente, S., Dellino, G. I., Faretta, M., Pelicci, P. G., Lania, L., & Majello, B. (2016). Cell cycle-dependent resolution of DNA double-strand breaks. Oncotarget, 7(4), 4949-4960. https://doi.org/10.18632/oncotarget.6644