Persistent repair intermediates induce senescence

. 2018 Sep 25 ; 9 (1) : 3923. [epub] 20180925

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid30254262

Grantová podpora
NKI 2014-6787 KWF Kankerbestrijding (Dutch Cancer Society) - International
NKI 2014-6787 KWF Kankerbestrijding (Dutch Cancer Society) - International
16-19437S Grantová Agentura České Republiky (Grant Agency of the Czech Republic) - International

Odkazy

PubMed 30254262
PubMed Central PMC6156224
DOI 10.1038/s41467-018-06308-9
PII: 10.1038/s41467-018-06308-9
Knihovny.cz E-zdroje

Double-stranded DNA breaks activate a DNA damage checkpoint in G2 phase to trigger a cell cycle arrest, which can be reversed to allow for recovery. However, damaged G2 cells can also permanently exit the cell cycle, going into senescence or apoptosis, raising the question how an individual cell decides whether to recover or withdraw from the cell cycle. Here we find that the decision to withdraw from the cell cycle in G2 is critically dependent on the progression of DNA repair. We show that delayed processing of double strand breaks through HR-mediated repair results in high levels of resected DNA and enhanced ATR-dependent signalling, allowing p21 to rise to levels at which it drives cell cycle exit. These data imply that cells have the capacity to discriminate breaks that can be repaired from breaks that are difficult to repair at a time when repair is still ongoing.

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