The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5'-to-3' resection of Double-Strand DNA Breaks (DSBs). Extended 3' single stranded DNA filaments can be exposed from a DSB through the redundant activities of the Exo1 nuclease and the Dna2 nuclease with the Sgs1 helicase. In the absence of Sae2, Mre11 binding to a DSB is prolonged, the two DNA ends cannot be kept tethered, and the DSB is not efficiently repaired. Here we show that deletion of the yeast 53BP1-ortholog RAD9 reduces Mre11 binding to a DSB, leading to Rad52 recruitment and efficient DSB end-tethering, through an Sgs1-dependent mechanism. As a consequence, deletion of RAD9 restores DSB repair either in absence of Sae2 or in presence of a nuclease defective MRX complex. We propose that, in cells lacking Sae2, Rad9/53BP1 contributes to keep Mre11 bound to a persistent DSB, protecting it from extensive DNA end resection, which may lead to potentially deleterious DNA deletions and genome rearrangements.
Functional Interplay between the 53BP1-Ortholog Rad9 and the Mre11 Complex Regulates Resection, End-Tethering and Repair of a Double-Strand Break / M. Ferrari, D. Dibitetto, G. De Gregorio, V.V. Eapen, C.C. Rawal, F. Lazzaro, M. Tsabar, F. Marini, J.E. Haber, A. Pellicioli. - In: PLOS GENETICS. - ISSN 1553-7404. - 11:1(2015 Jan 08), pp. e1004928.1-e1004928.14.
|Titolo:||Functional Interplay between the 53BP1-Ortholog Rad9 and the Mre11 Complex Regulates Resection, End-Tethering and Repair of a Double-Strand Break|
FERRARI, MATTEO (Primo)
DIBITETTO, DIEGO (Secondo)
PELLICIOLI, ACHILLE (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Progetto:||Roles of polo-like kinases in checkpoint adaptation and cell division in response to DNA damage|
|Data di pubblicazione:||8-gen-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pgen.1004928|
|Appare nelle tipologie:||01 - Articolo su periodico|