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TitleChromatin binding by HORMAD proteins regulates meiotic recombination initiation.
Journal, issue, pagesEMBO J, Vol. 43, Issue 5, Page 836-867, Year 2024
Publish dateFeb 8, 2024
AuthorsCarolyn R Milano / Sarah N Ur / Yajie Gu / Jessie Zhang / Rachal Allison / George Brown / Matthew J Neale / Eelco C Tromer / Kevin D Corbett / Andreas Hochwagen /
PubMed AbstractThe 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 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.
External linksEMBO J / PubMed:38332377 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.599 - 2.74 Å
Structure data

27030

8cww

EMDB-27030, PDB-8cww:
Structure of S. cerevisiae Hop1 CBR bound to a nucleosome
Method: EM (single particle) / Resolution: 2.74 Å

27096

8cze

EMDB-27096, PDB-8cze:
Structure of a Xenopus Nucleosome with Widom 601 DNA
Method: EM (single particle) / Resolution: 2.58 Å

PDB-7uba:
Structure of fungal Hop1 CBR domain
Method: X-RAY DIFFRACTION / Resolution: 1.599 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MES:
2-(N-MORPHOLINO)-ETHANESULFONIC ACID / pH buffer*YM / MES (buffer)

ChemComp-1PE:
PENTAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-HOH:
WATER / Water

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • xenopus laevis (African clawed frog)
  • escherichia coli (E. coli)
  • vanderwaltozyma polyspora dsm 70294 (fungus)
KeywordsDNA BINDING PROTEIN / meiosis / HORMAD / PHD / winged helix / DNA BINDING PROTEIN/DNA / recombination / chromosome axis / nucleosome / DNA BINDING PROTEIN-DNA complex

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