Journal Article

Structure and function of the Orc1 BAH-nucleosome complex

Leon, Victor A., Wang, Miao, Kuang, Zheng, De Ioannes, Pablo, Hochwagen, Andreas, Armache, Karim-Jean, Boeke, Jef D.

2019

Overview

The Origin Recognition Complex (ORC) is essential for replication, heterochromatin formation, telomere maintenance and genome stability in eukaryotes. Here we present the structure of the yeast Orc1 BAH domain bound to the nucleosome core particle. Our data reveal that Orc1, unlike its close homolog Sir3 involved in gene silencing, does not appear to discriminate between acetylated and non-acetylated lysine 16, modification states of the histone H4 tail that specify open and closed chromatin respectively. We elucidate the mechanism for this unique feature of Orc1 and hypothesize that its ability to interact with nucleosomes regardless of K16 modification state enables it to perform critical functions in both hetero- and euchromatin. We also show that direct interactions with nucleosomes are essential for Orc1 to maintain the integrity of rDNA borders during meiosis, a process distinct and independent from its known roles in silencing and replication. The Origin Recognition Complex (ORC) plays conserved and diverse roles in eukaryotes. Here the authors present the structure of a chromatin interacting domain of yeast Orc1 in complex with the nucleosome core particle, revealing that Orc1 interacts with the histone H4 tail irrespective of K16 acetylation; a modification that regulates accessibility to chromatin.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337/100/101 / 631/337/100/1701 / 631/337/100/2285 / 631/337/1427/2122 / 631/45/535/1266 / 82/16 / 82/29 / 82/80 / 82/83 / Adapter proteins / BASIC BIOLOGICAL SCIENCES / Biochemistry / Cell Cycle / Chromatin / Chromatin Assembly and Disassembly / chromatin structure / Core particles / double-strand DNA breaks / Epigenetics / Euchromatin / Euchromatin - genetics / Euchromatin - metabolism / Eukaryotes / Gene silencing / Genomes / Heterochromatin / Heterochromatin - genetics / Heterochromatin - metabolism / Histone H4 / histone post-translational modifications / Histones - genetics / Histones - metabolism / Homology / Humanities and Social Sciences / Lysine / Meiosis / multidisciplinary / Mutation / Nucleosomes / Nucleosomes - genetics / Nucleosomes - metabolism / Origin recognition complex / Origin Recognition Complex - chemistry / Origin Recognition Complex - genetics / Origin Recognition Complex - metabolism / Protein Binding / Protein Domains / Replication / Roles / Saccharomyces cerevisiae - chemistry / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Science / Science (multidisciplinary) / Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics / Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism / Structure-function relationships / x-ray crystallography / Yeast