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Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

FromPaperPlayer biorxiv cell biology


Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

FromPaperPlayer biorxiv cell biology

ratings:
Length:
20 minutes
Released:
Mar 5, 2023
Format:
Podcast episode

Description

Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.03.04.531117v1?rss=1

Authors: Milano, C. R., Ur, S. N., Gu, Y., Tromer, E. C., Zhang, J., Hochwagen, A., Corbett, K. D.

Abstract:
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 enrichment of axis proteins at nucleosome-rich genomic 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 loss of axis proteins from nucleosome-rich islands, reduces meiotic DNA double-strand breaks (DSBs), and leads to defects in chromosome synapsis. Synthetic effects with the disassemblase 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 this domain, suggesting that these mechanisms are broadly conserved.

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Released:
Mar 5, 2023
Format:
Podcast episode

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