Title | Compartmentalization of telomeres through DNA-scaffolded phase separation. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Jack, A, Kim, Y, Strom, AR, Lee, DSW, Williams, B, Schaub, JM, Kellogg, EH, Finkelstein, IJ, Ferro, LS, Yildiz, A, Brangwynne, CP |
Journal | Dev Cell |
Volume | 57 |
Issue | 2 |
Pagination | 277-290.e9 |
Date Published | 2022 Jan 24 |
ISSN | 1878-1551 |
Keywords | Cell Line, Chromatin, DNA, DNA Damage, DNA Repair, Humans, Optogenetics, Protein Binding, Shelterin Complex, Telomere, Telomere-Binding Proteins, Telomeric Repeat Binding Protein 1, Telomeric Repeat Binding Protein 2 |
Abstract | <p>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.</p> |
DOI | 10.1016/j.devcel.2021.12.017 |
Alternate Journal | Dev Cell |
PubMed ID | 35077681 |
PubMed Central ID | PMC8988007 |
Grant List | F31 GM123655 / GM / NIGMS NIH HHS / United States R35 GM136414 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States R01 GM120554 / GM / NIGMS NIH HHS / United States U01 DA040601 / DA / NIDA NIH HHS / United States K99 GM124463 / GM / NIGMS NIH HHS / United States R00 GM124463 / GM / NIGMS NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R01 GM118773 / GM / NIGMS NIH HHS / United States |