The DNA damage checkpoint (DDC) pathway is activated in response to DNA lesions and replication stress preserving the integrity of the genome. However, hyperactivation of DDC is detrimental to the cell, because it might prevent cell cycle restart after repair. Double strand DNA breaks (DSBs) are among the most deleterious types of damage occurring in the genome, as failure to repair these lesions can lead to genetic instability. In budding yeast, a key player during DSB metabolism is Rad9, an ortholog of human 53BP1. At DSBs and uncapped telomeres, Rad9 acts at the same time as a checkpoint adaptor and as a physical inhibitor of DNA resection. Recent evidences indicated that the Slx4-Rtt107 complex counteracts Rad9 binding to its partners Dpb11 and γ-H2AX, dampening the DDC after replication stress. Moreover, in the absence of Slx4, cells accumulate unresolved joint molecules and persistent DNA damage. Here we show that a cooperation of the scaffold proteins Slx4 and Rtt107 limits Rad9-dependent checkpoint signaling at DSBs and at uncapped telomeres. In the absence of Slx4 or Rtt107, Rad9 binding near an irreparable DSB is increased, leading to a robust checkpoint signaling and a slower resection. Importantly, the removal of the Slx4-Rtt107 complex in the sae2Δ cells exacerbates all these phenotypes, causing also severe defect in DSB repair. Our study sheds new light on the molecular mechanism that coordinates processing and repair of DSBs with the DNA damage checkpoint signalling.
Slx4 and rtt107 control checkpoint signaling and DNA resection at double-strand breaks / A. Pellicioli, D. Dibitetto, M. Ferrari, C. Rawal, F. Marini. ((Intervento presentato al convegno The DNA damage Response in cell physiology and disease tenutosi a Cape Sounio nel 2015.
|Titolo:||Slx4 and rtt107 control checkpoint signaling and DNA resection at double-strand breaks|
PELLICIOLI, ACHILLE (Corresponding)
DIBITETTO, DIEGO (Secondo)
RAWAL, CHETAN (Penultimo)
MARINI, FEDERICA (Ultimo)
|Data di pubblicazione:||5-ott-2015|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Citazione:||Slx4 and rtt107 control checkpoint signaling and DNA resection at double-strand breaks / A. Pellicioli, D. Dibitetto, M. Ferrari, C. Rawal, F. Marini. ((Intervento presentato al convegno The DNA damage Response in cell physiology and disease tenutosi a Cape Sounio nel 2015.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|