SWR1 and INO80 chromatin remodelers contribute to dna double-strand break perinuclear anchorage site choice

Chihiro Horigome, Yukako Oma, Tatsunori Konishi, Roger Schmid, Isabella Marcomini, Michael H. Hauer, Vincent Dion, Masahiko Harata, Susan M. Gasser

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery in budding yeast. Both the Nup84 pore subcomplex and Mps3, an innernuclear membrane (INM) SUN domain protein, have been implicated in DSB binding. It was unclear what, if anything, distinguishes the two potential sites of repair. Here, we characterize and distinguish thetwo binding sites. First, DSB-pore interaction occurs independently of cell-cycle phase and requires neither the chromatin remodeler INO80 nor recombinase Rad51 activity. In contrast, Mps3 binding is Sand G2 phase specific and requires both factors. SWR1-dependent incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in both G1- and S-phase cells. Importantly, functional assays indicate that mutations in the two sites have additive repair defects, arguing that the two perinuclear anchorage sites define distinct survival pathways.

Original languageEnglish
Pages (from-to)626-639
Number of pages14
JournalMolecular Cell
Volume55
Issue number4
DOIs
Publication statusPublished - 2014 Aug 21

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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