Single-stranded nucleic acid binding and coacervation by linker histone H1.

Autor: Leicher R; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA.; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA., Osunsade A; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA.; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA., Chua GNL; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA.; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA., Faulkner SC; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA., Latham AP; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., Watters JW; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA., Nguyen T; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA.; Tri-Institutional MD-PhD Program, New York, NY, USA., Beckwitt EC; Laboratory of DNA Replication, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA., Christodoulou-Rubalcava S; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA., Young PG; Tri-Institutional MD-PhD Program, New York, NY, USA., Zhang B; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., David Y; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA. davidshy@mskcc.org.; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA. davidshy@mskcc.org.; Tri-Institutional MD-PhD Program, New York, NY, USA. davidshy@mskcc.org.; Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA. davidshy@mskcc.org.; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medical College, New York, NY, USA. davidshy@mskcc.org., Liu S; Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA. shixinliu@rockefeller.edu.; Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA. shixinliu@rockefeller.edu.; Tri-Institutional MD-PhD Program, New York, NY, USA. shixinliu@rockefeller.edu.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2022 May; Vol. 29 (5), pp. 463-471. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1038/s41594-022-00760-4
Abstrakt: The H1 linker histone family is the most abundant group of eukaryotic chromatin-binding proteins. However, their contribution to chromosome structure and function remains incompletely understood. Here we use single-molecule fluorescence and force microscopy to directly visualize the behavior of H1 on various nucleic acid and nucleosome substrates. We observe that H1 coalesces around single-stranded DNA generated from tension-induced DNA duplex melting. Using a droplet fusion assay controlled by optical tweezers, we find that single-stranded nucleic acids mediate the formation of gel-like H1 droplets, whereas H1-double-stranded DNA and H1-nucleosome droplets are more liquid-like. Molecular dynamics simulations reveal that multivalent and transient engagement of H1 with unpaired DNA strands drives their enhanced phase separation. Using eGFP-tagged H1, we demonstrate that inducing single-stranded DNA accumulation in cells causes an increase in H1 puncta that are able to fuse. We further show that H1 and Replication Protein A occupy separate nuclear regions, but that H1 colocalizes with the replication factor Proliferating Cell Nuclear Antigen, particularly after DNA damage. Overall, our results provide a refined perspective on the diverse roles of H1 in genome organization and maintenance, and indicate its involvement at stalled replication forks.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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