Correlation Engine 2.0
Clear Search sequence regions

  • camptothecin (2)
  • cell (2)
  • cell cycle (3)
  • dna (4)
  • dna break (5)
  • dna damage (2)
  • dna repair enzymes (2)
  • Dpb11 (1)
  • endodeoxyribonucleases (2)
  • endonucleases (2)
  • methyl (2)
  • MUS81 (1)
  • nuclear proteins (2)
  • nucleic acids (1)
  • phenotypes (1)
  • RAD1 (1)
  • Rad9 (2)
  • rad9 protein (1)
  • research (1)
  • Rtt107 (5)
  • SAE2 (1)
  • signal (1)
  • SLX1 (1)
  • SLX4 (5)
  • Sizes of these terms reflect their relevance to your search.

    The DNA damage checkpoint pathway is activated in response to DNA lesions and replication stress to preserve genome integrity. However, hyper-activation of this surveillance system is detrimental to the cell, because it might prevent cell cycle re-start after repair, which may also lead to senescence. Here we show that the scaffold proteins Slx4 and Rtt107 limit checkpoint signalling at a persistent double-strand DNA break (DSB) and at uncapped telomeres. We found that Slx4 is recruited within a few kilobases of an irreparable DSB, through the interaction with Rtt107 and the multi-BRCT domain scaffold Dpb11. In the absence of Slx4 or Rtt107, Rad9 binding near the irreparable DSB is increased, leading to robust checkpoint signalling and slower nucleolytic degradation of the 5' strand. Importantly, in slx4Δ sae2Δ double mutant cells these phenotypes are exacerbated, causing a severe Rad9-dependent defect in DSB repair. Our study sheds new light on the molecular mechanism that coordinates the processing and repair of DSBs with DNA damage checkpoint signalling, preserving genome integrity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.


    Diego Dibitetto, Matteo Ferrari, Chetan C Rawal, Attila Balint, TaeHyung Kim, Zhaolei Zhang, Marcus B Smolka, Grant W Brown, Federica Marini, Achille Pellicioli. Slx4 and Rtt107 control checkpoint signalling and DNA resection at double-strand breaks. Nucleic acids research. 2016 Jan 29;44(2):669-82

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 26490958

    View Full Text