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Title: Columnar structure of human telomeric chromatin
Authors: Soman, Aghil
Wong, Sook Yi
Korolev, Nikolay
Surya, Wahyu
Lattmann, Simon
Vogirala, Vinod Kumar
Chen, Qinming
Berezhnoy, Nikolay V.
van Noort, John
Rhodes, Daniela
Nordenskiöld, Lars
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Soman, A., Wong, S. Y., Korolev, N., Surya, W., Lattmann, S., Vogirala, V. K., Chen, Q., Berezhnoy, N. V., van Noort, J., Rhodes, D. & Nordenskiöld, L. (2022). Columnar structure of human telomeric chromatin. Nature, 609(7929), 1048-1055.
Project: MOE2018-T2-1-112
Journal: Nature
Abstract: Telomeres, the ends of eukaryotic chromosomes, play pivotal parts in ageing and cancer and are targets of DNA damage and the DNA damage response1-5. Little is known about the structure of telomeric chromatin at the molecular level. Here we used negative stain electron microscopy and single-molecule magnetic tweezers to characterize 3-kbp-long telomeric chromatin fibres. We also obtained the cryogenic electron microscopy structure of the condensed telomeric tetranucleosome and its dinucleosome unit. The structure displayed close stacking of nucleosomes with a columnar arrangement, and an unusually short nucleosome repeat  length that comprised about 132 bp DNA wound in a continuous superhelix around histone octamers. This columnar structure is primarily stabilized by the H2A carboxy-terminal and histone amino-terminal tails in a synergistic manner. The columnar conformation results in exposure of the DNA helix, which may make it susceptible to both DNA damage and the DNA damage response. The conformation also exists in an alternative open state, in which one nucleosome is unstacked and flipped out, which exposes the acidic patch of the histone surface. The structural features revealed in this work suggest mechanisms by which protein factors involved in telomere maintenance can access telomeric chromatin in its compact form.
ISSN: 0028-0836
DOI: 10.1038/s41586-022-05236-5
Schools: School of Biological Sciences 
Research Centres: Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) 
NTU Institute of Structural Biology 
Rights: © 2022 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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