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TitleColumnar structure of human telomeric chromatin.
Journal, issue, pagesNature, Vol. 609, Issue 7929, Page 1048-1055, Year 2022
Publish dateSep 14, 2022
AuthorsAghil Soman / Sook Yi Wong / Nikolay Korolev / Wahyu Surya / Simon Lattmann / Vinod K Vogirala / Qinming Chen / Nikolay V Berezhnoy / John van Noort / Daniela Rhodes / Lars Nordenskiöld /
PubMed AbstractTelomeres, the ends of eukaryotic chromosomes, play pivotal parts in ageing and cancer and are targets of DNA damage and the DNA damage response. Little is known about the structure of telomeric ...Telomeres, the ends of eukaryotic chromosomes, play pivotal parts in ageing and cancer and are targets of DNA damage and the DNA damage response. 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.
External linksNature / PubMed:36104563
MethodsEM (single particle)
Resolution3.5 - 14.0 Å
Structure data

EMDB-31806, PDB-7v90:
Telomeric mononucleosome
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-31810, PDB-7v96:
Telomeric Dinucleosome
Method: EM (single particle) / Resolution: 3.92 Å

EMDB-31815, PDB-7v9c:
Telomeric Dinucleosome in open state
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-31816, PDB-7v9j:
Telomeric trinucleosome
Method: EM (single particle) / Resolution: 8.0 Å

EMDB-31823, PDB-7v9k:
Telomeric tetranucleosome
Method: EM (single particle) / Resolution: 8.1 Å

EMDB-31826, PDB-7v9s:
Telomeric trinucleosome in open state
Method: EM (single particle) / Resolution: 11.0 Å

EMDB-31832, PDB-7va4:
Telomeric tetranucleosome in open state
Method: EM (single particle) / Resolution: 14.0 Å

EMDB-31907: Telomeric Dinucleosome at 4.6 angstroms
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-31908: Telomeric Dinucleosome at 5angstroms
Method: EM (single particle) / Resolution: 5.0 Å

EMDB-31909: Open dinucleosome at 6.6 angstroms
Method: EM (single particle) / Resolution: 6.7 Å

Source
  • homo sapiens (human)
KeywordsDNA BINDING PROTEIN/DNA / Telomere / nucleosome / chromatin / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex

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