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Chromatin remodeler Fun30 facilitates the relocation of persistent DNA double-strand breaks to the nuclear periphery

  • Mehwish Iqbal
  • , Jisha Chalissery
  • , Amira Bekdash
  • , Asma Alnuaimi
  • , Ahmed H. Hassan
  • United Arab Emirates University

Research output: Contribution to journalArticlepeer-review

Abstract

DNA double-strand break (DSB) repair is critical for genome stability and requires chromatin remodeling for efficient processing. Fun30, an ATP-dependent chromatin remodeler, promotes long-range DNA end resection to generate 3′ overhangs, a key step in homologous recombination. Persistent DSBs relocate to the nuclear periphery, particularly through interactions with the inner nuclear membrane protein Mps3 and the nuclear pore complex component Nup84. By tracking a single irreparable break, we show that Fun30 facilitates this relocation. In fun30Δ cells, Mps3 and Nup84 enrichment at DSBs was reduced, indicating impaired tethering. We further demonstrate that Fun30 promotes deposition of the histone variant H2A.Z at DSBs. Thus, Fun30 favors relocation of persistent DSBs to the nuclear periphery by supporting resection and H2A.Z incorporation.

Original languageEnglish
Pages (from-to)439-450
Number of pages12
JournalFEBS Letters
Volume600
Issue number4
DOIs
StatePublished - Feb 2026

Keywords

  • DNA repair
  • Fun30
  • chromatin remodeling
  • nuclear envelope
  • resection

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