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-Structure paper
タイトル | Chromatin binding by HORMAD proteins regulates meiotic recombination initiation. |
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ジャーナル・号・ページ | EMBO J, Vol. 43, Issue 5, Page 836-867, Year 2024 |
掲載日 | 2024年2月8日 |
著者 | 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 / |
PubMed 要旨 | 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 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. |
リンク | EMBO J / PubMed:38332377 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.599 - 2.74 Å |
構造データ | EMDB-27030, PDB-8cww: EMDB-27096, PDB-8cze: PDB-7uba: |
化合物 | ChemComp-ZN: ChemComp-MES: ChemComp-1PE: ChemComp-PG4: ChemComp-HOH: |
由来 |
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キーワード | DNA BINDING PROTEIN (DNA結合タンパク質) / meiosis (減数分裂) / HORMAD / PHD / winged helix / DNA BINDING PROTEIN/DNA / recombination (遺伝的組換え) / chromosome axis / nucleosome (ヌクレオソーム) / DNA BINDING PROTEIN-DNA complex |