Shelterin Components Modulate Nucleic Acids Condensation and Phase Separation in the Context of Telomeric DNA

Andrea Soranno, J. Jeremías Incicco, Paolo De Bona, Eric J. Tomko, Eric A. Galburt, Alex S. Holehouse, Roberto Galletto

Research output: Contribution to journalArticlepeer-review

Abstract

Telomeres are nucleoprotein complexes that protect the ends of chromosomes and are essential for chromosome stability in Eukaryotes. In cells, individual telomeres form distinct globules of finite size that appear to be smaller than expected for bare DNA. Moreover, telomeres can cluster together, form telomere-induced-foci or co-localize with promyelocytic leukemia (PML) nuclear bodies. The physical basis for collapse of individual telomeres and coalescence of multiple ones remains unclear, as does the relationship between these two phenomena. By combining single-molecule force spectroscopy measurements, optical microscopy, turbidity assays, and simulations, we show that the telomere scaffolding protein TRF2 can condense individual DNA chains and drives coalescence of multiple DNA molecules, leading to phase separation and the formation of liquid-like droplets. Addition of the TRF2 binding protein hRap1 modulates phase boundaries and tunes the specificity of solution demixing while simultaneously altering the degree of DNA compaction. Our results suggest that the condensation of single telomeres and formation of biomolecular condensates containing multiple telomeres are two different outcomes driven by the same set of molecular interactions. Moreover, binding partners, such as other telomere components, can alter those interactions to promote single-chain DNA compaction over multiple-chain phase separation.

Original languageEnglish
Article number167685
JournalJournal of Molecular Biology
Volume434
Issue number16
DOIs
StatePublished - Aug 30 2022

Keywords

  • DNA condensation
  • Phase separation
  • TRF2
  • Telomeres
  • hRap1

Fingerprint

Dive into the research topics of 'Shelterin Components Modulate Nucleic Acids Condensation and Phase Separation in the Context of Telomeric DNA'. Together they form a unique fingerprint.

Cite this