1. Academic Validation
  2. The 9-1-1 Complex Controls Mre11 Nuclease and Checkpoint Activation during Short-Range Resection of DNA Double-Strand Breaks

The 9-1-1 Complex Controls Mre11 Nuclease and Checkpoint Activation during Short-Range Resection of DNA Double-Strand Breaks

  • Cell Rep. 2020 Oct 20;33(3):108287. doi: 10.1016/j.celrep.2020.108287.
Elisa Gobbini 1 Erika Casari 1 Chiara Vittoria Colombo 1 Diego Bonetti 1 Maria Pia Longhese 2
Affiliations

Affiliations

  • 1 Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano 20126, Italy.
  • 2 Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano 20126, Italy. Electronic address: mariapia.longhese@unimib.it.
Abstract

Homologous recombination is initiated by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process in which an initial short-range step is catalyzed by the Mre11-Rad50-Xrs2 (MRX) complex and limited to the vicinity of the DSB end. Then the two long-range resection Exo1 and Dna2-Sgs1 nucleases extend the resected DNA tracts. How short-range resection is regulated and contributes to checkpoint activation remains to be determined. Here, we show that abrogation of long-range resection induces a checkpoint response that decreases DNA damage resistance. This checkpoint depends on the 9-1-1 complex, which recruits Dpb11 and Rad9 at damaged DNA. Furthermore, the 9-1-1 complex, independently of Dpb11 and Rad9, restricts short-range resection by negatively regulating Mre11 Nuclease. We propose that 9-1-1, which is loaded at the leading edge of resection, plays a key function in regulating Mre11 Nuclease and checkpoint activation once DSB resection is initiated.

Keywords

9-1-1; DNA damage; Dpb11/TopBP1; MRX/MRN; Rad9/53BP1; S. cerevisiae; checkpoint; double-strand breaks; resection.

Figures
Products