Compartmentalization of telomeres through DNA-scaffolded phase separation.

Autor:	Jack A; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA., Kim Y; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Strom AR; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Lee DSW; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA., Williams B; Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA., Schaub JM; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA., Kellogg EH; Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA., Finkelstein IJ; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX 78712, USA., Ferro LS; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: ferro@berkeley.edu., Yildiz A; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Physics Department, University of California, Berkeley, CA 94720, USA. Electronic address: yildiz@berkeley.edu., Brangwynne CP; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Howard Hughes Medical Institute, Princeton University, Princeton NJ 08544, USA. Electronic address: cbrangwy@princeton.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2022 Jan 24; Vol. 57 (2), pp. 277-290.e9.
DOI:	10.1016/j.devcel.2021.12.017
Abstrakt:	Telomeres form unique nuclear compartments that prevent degradation and fusion of chromosome ends by recruiting shelterin proteins and regulating access of DNA damage repair factors. To understand how these dynamic components protect chromosome ends, we combine in vivo biophysical interrogation and in vitro reconstitution of human shelterin. We show that shelterin components form multicomponent liquid condensates with selective biomolecular partitioning on telomeric DNA. Tethering and anomalous diffusion prevent multiple telomeres from coalescing into a single condensate in mammalian cells. However, telomeres coalesce when brought into contact via an optogenetic approach. TRF1 and TRF2 subunits of shelterin drive phase separation, and their N-terminal domains specify interactions with telomeric DNA in vitro. Telomeric condensates selectively recruit telomere-associated factors and regulate access of DNA damage repair factors. We propose that shelterin mediates phase separation of telomeric chromatin, which underlies the dynamic yet persistent nature of the end-protection mechanism. Competing Interests: Declaration of interests C.P.B. is a founder of and consultant for Nereid Therapeutics. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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