DNA Local-Flexibility-Dependent Assembly of Phase-Separated Liquid Droplets
Phase separation of intracellular components has been recently realized as a mechanism by which cells achieve membraneless organization. Here, we study the associative liquid-liquid phase separation (LLPS) of DNA upon complexation with cationic polypeptides. Comparing the phase behavior of different...
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| Veröffentlicht in: | Biophysical journal 2018-11, Vol.115 (10), p.1840-1847 |
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| creator | Shakya, Anisha King, John T. |
| description | Phase separation of intracellular components has been recently realized as a mechanism by which cells achieve membraneless organization. Here, we study the associative liquid-liquid phase separation (LLPS) of DNA upon complexation with cationic polypeptides. Comparing the phase behavior of different single-stranded DNA as well as double-stranded DNA (dsDNA) sequences that differ in persistence lengths, we find that DNA local flexibility, not simply charge density, determines the LLPS. Furthermore, in a nucleotide- and DNA-dependent manner, free nucleotide triphosphates promote LLPS of polypeptide-dsDNA complexes that are otherwise prone to precipitation. Under these conditions, dsDNA undergoes a secondary phase separation forming liquid-crystalline subcompartments inside the droplets. These results point toward a role of local DNA flexibility, encoded in the sequence, in the regulation and selectivity of multicomponent LLPS in membraneless intracellular organization. |
| doi_str_mv | 10.1016/j.bpj.2018.09.022 |
| format | Article |
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These results point toward a role of local DNA flexibility, encoded in the sequence, in the regulation and selectivity of multicomponent LLPS in membraneless intracellular organization.</description><subject>Base Sequence</subject><subject>DNA - chemistry</subject><subject>DNA - genetics</subject><subject>DNA, Single-Stranded - chemistry</subject><subject>DNA, Single-Stranded - genetics</subject><subject>Hydrodynamics</subject><subject>Liquid Crystals - chemistry</subject><subject>Models, Molecular</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleic Acids and Genome Biophysics</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1P4zAUtNAiKB8_gMsqx70kPCe2kwgJqaKwi7YCJOBsOfbL4sqNg50i-u9JVUDshdM7vJl582YIOaGQUaDidJE1_SLLgVYZ1Bnk-Q6ZUM7yFKASP8gEAERasJrvk4MYFwA050D3yH4BBctLJibk7-xmmsy9Vi69cvhqG-vssE5n2GNnsBuSaYy4bNw68W1y96QipvfYq6AGNMncPq-sSWbB9w6HeER2W-UiHr_PQ_J4dflw8Sed3_6-vpjOU804HdKaaVFCoTkVgKpV1DSF4Rx5Baw0ogDRtrWCypiyNDVvjSpKVle60dSwFsrikJxvdftVs0SjR5tBOdkHu1RhLb2y8v9NZ5_kP_8ixeZvmo8Cv94Fgn9eYRzk0kaNzqkO_SrKnAoOpYCaj1C6hergYwzYfp6hIDclyIUcS5CbEiTUcixh5Pz86u-T8ZH6CDjbAnBM6cVikFFb7DQaG1AP0nj7jfwbroyYRA</recordid><startdate>20181120</startdate><enddate>20181120</enddate><creator>Shakya, Anisha</creator><creator>King, John T.</creator><general>Elsevier Inc</general><general>The Biophysical Society</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181120</creationdate><title>DNA Local-Flexibility-Dependent Assembly of Phase-Separated Liquid Droplets</title><author>Shakya, Anisha ; King, John T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-94c6703c5160eafa1db3d55e58047d6306ff9a08dd77d95fda37498cbc1d4f073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Base Sequence</topic><topic>DNA - chemistry</topic><topic>DNA - genetics</topic><topic>DNA, Single-Stranded - chemistry</topic><topic>DNA, Single-Stranded - genetics</topic><topic>Hydrodynamics</topic><topic>Liquid Crystals - chemistry</topic><topic>Models, Molecular</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic Acids and Genome Biophysics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shakya, Anisha</creatorcontrib><creatorcontrib>King, John T.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shakya, Anisha</au><au>King, John T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Local-Flexibility-Dependent Assembly of Phase-Separated Liquid Droplets</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2018-11-20</date><risdate>2018</risdate><volume>115</volume><issue>10</issue><spage>1840</spage><epage>1847</epage><pages>1840-1847</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>Phase separation of intracellular components has been recently realized as a mechanism by which cells achieve membraneless organization. Here, we study the associative liquid-liquid phase separation (LLPS) of DNA upon complexation with cationic polypeptides. Comparing the phase behavior of different single-stranded DNA as well as double-stranded DNA (dsDNA) sequences that differ in persistence lengths, we find that DNA local flexibility, not simply charge density, determines the LLPS. Furthermore, in a nucleotide- and DNA-dependent manner, free nucleotide triphosphates promote LLPS of polypeptide-dsDNA complexes that are otherwise prone to precipitation. Under these conditions, dsDNA undergoes a secondary phase separation forming liquid-crystalline subcompartments inside the droplets. 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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Base Sequence DNA - chemistry DNA - genetics DNA, Single-Stranded - chemistry DNA, Single-Stranded - genetics Hydrodynamics Liquid Crystals - chemistry Models, Molecular Nucleic Acid Conformation Nucleic Acids and Genome Biophysics |
| title | DNA Local-Flexibility-Dependent Assembly of Phase-Separated Liquid Droplets |
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