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 language | English |
|---|---|
| Pages (from-to) | 4949-4960 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- AsiSI restriction enzyme
- Cell-cycle
- DSB repair
- Site-specific DSBs
ASJC Scopus subject areas
- Oncology
Cite this
Cell cycle-dependent resolution of DNA double-strand breaks. / Ambrosio, Susanna; Di Palo, Giacomo; Napolitano, Giuliana; Amente, Stefano; Dellino, Gaetano Ivan; Faretta, Mario; Pelicci, Pier Giuseppe; Lania, Luigi; Majello, Barbara.
In: Oncotarget, Vol. 7, No. 4, 2016, p. 4949-4960.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cell cycle-dependent resolution of DNA double-strand breaks
AU - Ambrosio, Susanna
AU - Di Palo, Giacomo
AU - Napolitano, Giuliana
AU - Amente, Stefano
AU - Dellino, Gaetano Ivan
AU - Faretta, Mario
AU - Pelicci, Pier Giuseppe
AU - Lania, Luigi
AU - Majello, Barbara
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - AsiSI restriction enzyme
KW - Cell-cycle
KW - DSB repair
KW - Site-specific DSBs
UR - http://www.scopus.com/inward/record.url?scp=84958025612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958025612&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6644
DO - 10.18632/oncotarget.6644
M3 - Article
AN - SCOPUS:84958025612
VL - 7
SP - 4949
EP - 4960
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 4
ER -