Slx4 and Rtt107 control checkpoint signalling and DNA resection at double-strand breaks

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