Details

Autor(en) / Beteiligte

• Ferrari, Matteo
• Dibitetto, Diego
• De Gregorio, Giuseppe
• Eapen, Vinay V
• Rawal, Chetan C
• Lazzaro, Federico
• Tsabar, Michael
• Marini, Federica
• Haber, James E
• Pellicioli, Achille
• Nitiss, John L.

Titel

Functional interplay between the 53BP1-ortholog Rad9 and the Mre11 complex regulates resection, end-tethering and repair of a double-strand break

Ist Teil von

• PLoS genetics, 2015-01, Vol.11 (1), p.e1004928-e1004928

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.