Functional Interplay between the 53BP1-Ortholog Rad9 and the Mre11 Complex Regulates Resection, End-Tethering and Repair of a Double-Strand Break

• DOI: 10.1371/journal.pgen.1004928
• Publication Date: 2015-01-08T19:20:23Z
• Authors: Matteo Ferrari; Diego Dibitetto; Giuseppe De Gregorio; Vinay V. Eapen; Chetan C. Rawal; Federico Lazzaro; Michael Tsabar; Federica Marini; James E. Haber; Achille Pellicioli
• Keywords: Tethering; Non-homologous end joining

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 filaments can be exposed from a DSB through redundant activities Exo1 and Dna2 Sgs1 helicase. In absence Mre11 binding to is prolonged, two ends cannot kept tethered, not efficiently repaired. Here we show that deletion yeast 53BP1-ortholog RAD9 reduces DSB, leading Rad52 recruitment efficient end-tethering, an Sgs1-dependent mechanism. As consequence, restores repair either in Sae2 or presence defective MRX complex. We propose that, cells lacking Rad9/53BP1 contributes keep bound persistent protecting it extensive end resection, which may lead potentially deleterious deletions genome rearrangements.