@article{3e7df76ab47e48ae99430203548fade0,
title = "Structure and function of the Orc1 BAH-nucleosome complex",
abstract = "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.",
author = "{De Ioannes}, Pablo and Leon, {Victor A.} and Zheng Kuang and Miao Wang and Boeke, {Jef D.} and Andreas Hochwagen and Armache, {Karim Jean}",
note = "Funding Information: We thank the staff of the NE-CAT beamline ID-24 at the Advanced Photon Source of Argonne National Laboratory for technical support during data collection; Dr. B. Ueberheide and staff scientists at the proteomics core facility at NYUMC for help with MS analyses, Dr. H. Neuman (Max Planck, Dortmund) for the His6-H3(Δ93–98)-TEV-H4 K16 amber codon expression vector and Dr. J. Chin (MRC, UK) for pAcKRS-3 plasmid; Drs. D. Reinberg (NYU) and G. Narlikar (UCSF) and members of the Armache Laboratory for helpful discussions. Work in K-J.A.{\textquoteright}s laboratory is supported by the David and Lucile Packard Foundation, and the NIH (R01GM115882). Work in A.H.{\textquoteright}s laboratory is supported by the grant R01GM111715. Work in J.B.{\textquoteright}s laboratory is supported by the grant U54GM103520. The mass spectrometric experiments were in part supported by the NYU School of Medicine and with a shared instrumentation grant from the NIH, 1S10OD010582-01A1, for the purchase of an Orbitrap Fusion Lumos. NE-CAT is supported by NIH grant 5P41GM103403 and APS is supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-10609-y",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}