The 53BP1-ortholog Rad9 is a master regulator of DNA double strand break processing and repair Matteo Ferrari, Diego Dibitetto, Chetan Rawal and Achille Pellicioli University of Milan, Milan, Italy DNA double strand breaks (DSBs) are among the most deleterious types of damage occurring in the genome. Failure to repair these lesions through either nonhomologous-end-joining (NHEJ) or homologous recombination (HR) leads to genome rearrangements. The 5’ strand of a DSB can be nucleolytically degraded by several nucleases and associated factors, including Mre11, CtIP/Sae2, Exo1 and Dna2 together with Bloom helicase/Sgs1, through a finely regulated process called DSB resection. Once resection is initiated, NHEJ is prevented and HR can take place. Several findings suggest that DSB resection is a double-edged sword, since on one hand it is needed for faithful HR, but on the other, it may lead to extensive DNA deletions associated with genome instability. Both in mammals and yeast, 53BP1/Rad9 protein binds near the lesion and counteracts the resection process, limiting the formation of single-strand DNA. By using S. cerevisiae as a model organism, we show that deletion of RAD9 reduces Mre11 binding to a DSB in sae2Δ cells through an Sgs1-dependent mechanism. This leads to efficient DSB end-tethering and repair. More recently, we also obtained additional results unrevealing novel insights on the regulatory role of Rad9 in DSB repair. Models will be presented to speculate how Rad9 controls DSB repair, preserving genome integrity.
The 53BP1-ortholog Rad9 is a master regulator of Double Strand break processing and repair / M. Ferrari, D. Dibitetto, C. Rawal, A. Pellicioli. ((Intervento presentato al convegno The DNA damage Response in cell physiology and disease tenutosi a Cape Sounio nel 2015.
|Titolo:||The 53BP1-ortholog Rad9 is a master regulator of Double Strand break processing and repair|
FERRARI, MATTEO (Primo)
DIBITETTO, DIEGO (Secondo)
PELLICIOLI, ACHILLE (Ultimo)
|Data di pubblicazione:||5-ott-2015|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Citazione:||The 53BP1-ortholog Rad9 is a master regulator of Double Strand break processing and repair / M. Ferrari, D. Dibitetto, C. Rawal, A. Pellicioli. ((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|