Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

Carolyn R. Milano, Sarah N. Ur, Yajie Gu, Jessie Zhang, Rachal Allison, George Brown, Matthew J. Neale, Eelco C. Tromer, Kevin D. Corbett, Andreas Hochwagen

Research output: Contribution to journalArticlepeer-review


The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. In S. cerevisiae, the HORMAD protein Hop1 mediates the enrichment of axis proteins at nucleosome-rich islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix–turn–helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes a localized reduction of axis protein binding and meiotic DNA double-strand breaks (DSBs) in axis islands and leads to defects in chromosome synapsis. Synthetic effects with mutants of the Hop1 regulator Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of the CBR, suggesting that the mechanisms we uncover are broadly conserved.

Original languageEnglish (US)
Pages (from-to)836-867
Number of pages32
JournalEMBO Journal
Issue number5
StatePublished - Mar 1 2024


  • Budding Yeast
  • Chromatin
  • Chromosome Segregation
  • Meiosis

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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