Shelterin Components Modulate Nucleic Acids Condensation and Phase Separation in the Context of Telomeric DNA. Issue 16 (30th August 2022)

• Record Type: Journal Article
• Authors: Soranno, Andrea; Incicco, J. Jeremías; De Bona, Paolo; Tomko, Eric J.; Galburt, Eric A.; Holehouse, Alex S.; Galletto, Roberto
• Is Part Of: Journal of molecular biology. Volume 434:Issue 16(2022)
• Publication Date: 2022-08-30
• Subjects: TRF2 -- hRap1 -- Phase separation -- DNA condensation -- Telomeres; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2022.167685
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: TRF2 condenses single DNA chains, while in the presence of multiple DNA chains the system undergoes phase separation. TRF2-dependent condensation of single nucleic acid molecules and phase separation of multiple ones are two physical processes driven by the same set of molecular interactions. Interaction of hRap1 with TRF2 modulates both DNA collapse and alters nucleic acid specificity in phase-separation. We speculate that the physical interactions that mediate phase separation and condensation represent a possible means for controlling access to and the state of telomeres. 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.