%0 Journal Article
%T Functional Interplay between the 53BP1-Ortholog Rad9 and the Mre11 Complex Regulates Resection, End-Tethering and Repair of a Double-Strand Break
%A Achille Pellicioli
%A Chetan C. Rawal
%A Diego Dibitetto
%A Federica Marini
%A Federico Lazzaro
%A Giuseppe De Gregorio
%A James E. Haber
%A Matteo Ferrari
%A Michael Tsabar
%A Vinay V. Eapen
%J -
%D 2015
%R 10.1371/journal.pgen.1004928
%X The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5กไ-to-3กไ resection of Double-Strand DNA Breaks (DSBs). Extended 3กไ 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
%K Surgical resection
%K Galactose
%K Cell binding
%K Non-homologous end joining
%K Nucleases
%K Cell cultures
%K DNA damage
%K DNA-binding proteins
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004928