{"entity": "researcher", "timestamp": "2026-08-09T07:36:41.521Z", "family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "affiliations": ["Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738"}}, "publications": [{"entity": "publication", "iuid": "c7b4c0e889ea4415b8cbaa01eccb847b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c7b4c0e889ea4415b8cbaa01eccb847b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c7b4c0e889ea4415b8cbaa01eccb847b"}}, "title": "ALC1 Finds a New Foothold on the Nucleosome\u2019s Super-Groove", "authors": [{"family": "Bridges", "given": "Hannah R", "initials": "HR", "orcid": "0000-0001-6890-6050", "researcher": {"href": "https://publications.scilifelab.se/researcher/87b42fbd72ad4a25949e7bb7113dd0b1.json"}}, {"family": "Bacic", "given": "Luka", "initials": "L", "orcid": "0000-0001-6896-3506", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bcd56cafd294116870c894ba344cf12.json"}}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}, {"family": "Gaullier", "given": "Guillaume", "initials": "G", "orcid": "0000-0003-3405-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/26bde2020c164cff8216338fb2d6d652.json"}}], "type": "posted-content", "published": "2025-11-10", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.11.10.687450", "pmid": null, "labels": {"Cryo-EM": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-17T10:09:15.163Z", "modified": "2025-12-18T18:59:43.530Z"}, {"entity": "publication", "iuid": "47741b433ff341d898259372903d7f89", "links": {"self": {"href": "https://publications.scilifelab.se/publication/47741b433ff341d898259372903d7f89.json"}, "display": {"href": "https://publications.scilifelab.se/publication/47741b433ff341d898259372903d7f89"}}, "title": "Massively parallel analysis of single-molecule dynamics on next-generation sequencing chips.", "authors": [{"family": "Aguirre Rivera", "given": "J", "initials": "J", "orcid": "0000-0002-5263-3577", "researcher": {"href": "https://publications.scilifelab.se/researcher/f164778943f24897a1fa31ac3c6fd2ce.json"}}, {"family": "Mao", "given": "G", "initials": "G", "orcid": "0000-0001-5841-0991", "researcher": {"href": "https://publications.scilifelab.se/researcher/827d755ddbd24c2ca839364c9e139965.json"}}, {"family": "Sabantsev", "given": "A", "initials": "A", "orcid": "0000-0002-8559-8894", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae73150df15e4730be688fc5137a1389.json"}}, {"family": "Panfilov", "given": "M", "initials": "M", "orcid": "0000-0003-2875-7315", "researcher": {"href": "https://publications.scilifelab.se/researcher/58d227ea91aa4b90915a7e2afeb9283e.json"}}, {"family": "Hou", "given": "Q", "initials": "Q", "orcid": "0009-0007-9296-4788", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1048338ae024e9fbc9d82d79f61ffee.json"}}, {"family": "Lindell", "given": "M", "initials": "M"}, {"family": "Chanez", "given": "C", "initials": "C", "orcid": "0000-0002-3432-4375", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ce66636fd1344819df3518ffa6406ce.json"}}, {"family": "Ritort", "given": "F", "initials": "F", "orcid": "0000-0002-4869-5003", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7a34940c8ae42f1a2381b0b48fe06be.json"}}, {"family": "Jinek", "given": "M", "initials": "M", "orcid": "0000-0002-7601-210X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b86b5f94bbf4b87849dd4d8cebf80f8.json"}}, {"family": "Deindl", "given": "S", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal article", "published": "2024-08-23", "journal": {"title": "Science", "issn": "1095-9203", "issn-l": "0036-8075", "volume": "385", "issue": "6711", "pages": "892-898"}, "abstract": "Single-molecule techniques are ideally poised to characterize complex dynamics but are typically limited to investigating a small number of different samples. However, a large sequence or chemical space often needs to be explored to derive a comprehensive understanding of complex biological processes. Here we describe multiplexed single-molecule characterization at the library scale (MUSCLE), a method that combines single-molecule fluorescence microscopy with next-generation sequencing to enable highly multiplexed observations of complex dynamics. We comprehensively profiled the sequence dependence of DNA hairpin properties and Cas9-induced target DNA unwinding-rewinding dynamics. The ability to explore a large sequence space for Cas9 allowed us to identify a number of target sequences with unexpected behaviors. We envision that MUSCLE will enable the mechanistic exploration of many fundamental biological processes.", "doi": "10.1126/science.adn5371", "pmid": "39172826", "labels": {"NGI Short read": "Technology development", "NGI Uppsala (SNP&SEQ Technology Platform)": "Technology development", "National Genomics Infrastructure": "Technology development"}, "xrefs": [], "notes": [], "created": "2024-08-23T12:11:46.194Z", "modified": "2024-11-05T18:25:16.868Z"}, {"entity": "publication", "iuid": "cc8ed21067814ac09b593e3f722678d2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cc8ed21067814ac09b593e3f722678d2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cc8ed21067814ac09b593e3f722678d2"}}, "title": "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.", "authors": [{"family": "Bacic", "given": "Luka", "initials": "L"}, {"family": "Gaullier", "given": "Guillaume", "initials": "G", "orcid": "0000-0003-3405-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/26bde2020c164cff8216338fb2d6d652.json"}}, {"family": "Mohapatra", "given": "Jugal", "initials": "J"}, {"family": "Mao", "given": "Guanzhong", "initials": "G"}, {"family": "Brackmann", "given": "Klaus", "initials": "K"}, {"family": "Panfilov", "given": "Mikhail", "initials": "M", "orcid": "0000-0003-2875-7315", "researcher": {"href": "https://publications.scilifelab.se/researcher/58d227ea91aa4b90915a7e2afeb9283e.json"}}, {"family": "Liszczak", "given": "Glen", "initials": "G"}, {"family": "Sabantsev", "given": "Anton", "initials": "A", "orcid": "0000-0002-8559-8894", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae73150df15e4730be688fc5137a1389.json"}}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal article", "published": "2024-02-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "1000", "issn-l": "2041-1723"}, "abstract": "The chromatin remodeler ALC1 is activated by DNA damage-induced poly(ADP-ribose) deposited by PARP1/PARP2 and their co-factor HPF1. ALC1 has emerged as a cancer drug target, but how it is recruited to ADP-ribosylated nucleosomes to affect their positioning near DNA breaks is unknown. Here we find that PARP1/HPF1 preferentially initiates ADP-ribosylation on the histone H2B tail closest to the DNA break. To dissect the consequences of such asymmetry, we generate nucleosomes with a defined ADP-ribosylated H2B tail on one side only. The cryo-electron microscopy structure of ALC1 bound to such an asymmetric nucleosome indicates preferential engagement on one side. Using single-molecule FRET, we demonstrate that this asymmetric recruitment gives rise to directed sliding away from the DNA linker closest to the ADP-ribosylation site. Our data suggest a mechanism by which ALC1 slides nucleosomes away from a DNA break to render it more accessible to repair factors.", "doi": "10.1038/s41467-024-45237-8", "pmid": "38307862", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10837151"}, {"db": "pii", "key": "10.1038/s41467-024-45237-8"}], "notes": [], "created": "2024-02-06T08:28:40.080Z", "modified": "2025-10-25T10:15:14.050Z"}, {"entity": "publication", "iuid": "0b42978dde96434c9ab07d794464b5fc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0b42978dde96434c9ab07d794464b5fc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0b42978dde96434c9ab07d794464b5fc"}}, "title": "Sequence specificity in DNA binding is mainly governed by association.", "authors": [{"family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "researcher": {"href": "https://publications.scilifelab.se/researcher/67842d62534d4612a5e92f7a275df4dc.json"}}, {"family": "Mao", "given": "Guanzhong", "initials": "G", "orcid": "0000-0001-5841-0991", "researcher": {"href": "https://publications.scilifelab.se/researcher/827d755ddbd24c2ca839364c9e139965.json"}}, {"family": "Yuan", "given": "Jinwen", "initials": "J", "orcid": "0000-0002-7442-9921", "researcher": {"href": "https://publications.scilifelab.se/researcher/a568fed6aa93423499feac15e50efcfe.json"}}, {"family": "Zikrin", "given": "Spartak", "initials": "S"}, {"family": "Abdurakhmanov", "given": "Eldar", "initials": "E"}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}, {"family": "Elf", "given": "Johan", "initials": "J", "orcid": "0000-0001-5522-1810", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8c05ef8453040a794cb9c716f0ef8d6.json"}}], "type": "journal article", "published": "2022-01-28", "journal": {"title": "Science", "issn": "1095-9203", "issn-l": "0036-8075", "volume": "375", "issue": "6579", "pages": "442-445"}, "abstract": "Sequence-specific binding of proteins to DNA is essential for accessing genetic information. We derive a model that predicts an anticorrelation between the macroscopic association and dissociation rates of DNA binding proteins. We tested the model for thousands of different lac operator sequences with a protein binding microarray and by observing kinetics for individual lac repressor molecules in single-molecule experiments. We found that sequence specificity is mainly governed by the efficiency with which the protein recognizes different targets. The variation in probability of recognizing different targets is at least 1.7 times as large as the variation in microscopic dissociation rates. Modulating the rate of binding instead of the rate of dissociation effectively reduces the risk of the protein being retained on nontarget sequences while searching.", "doi": "10.1126/science.abg7427", "pmid": "35084952", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-11-09T15:40:30.257Z", "modified": "2025-10-17T13:05:07.827Z"}, {"entity": "publication", "iuid": "0558978a6cc14afe8e55e57e9b14b996", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0558978a6cc14afe8e55e57e9b14b996.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0558978a6cc14afe8e55e57e9b14b996"}}, "title": "Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.", "authors": [{"family": "Bacic", "given": "Luka", "initials": "L", "orcid": "0000-0001-6896-3506", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bcd56cafd294116870c894ba344cf12.json"}}, {"family": "Gaullier", "given": "Guillaume", "initials": "G", "orcid": "0000-0003-3405-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/26bde2020c164cff8216338fb2d6d652.json"}}, {"family": "Sabantsev", "given": "Anton", "initials": "A", "orcid": "0000-0002-8559-8894", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae73150df15e4730be688fc5137a1389.json"}}, {"family": "Lehmann", "given": "Laura C", "initials": "LC", "orcid": "0000-0003-2518-5606", "researcher": {"href": "https://publications.scilifelab.se/researcher/e73ae6d30ebe4c68971f3b0908d061c6.json"}}, {"family": "Brackmann", "given": "Klaus", "initials": "K"}, {"family": "Dimakou", "given": "Despoina", "initials": "D", "orcid": "0000-0002-1424-5469", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba59232af334167a0574861f7e921ca.json"}}, {"family": "Halic", "given": "Mario", "initials": "M", "orcid": "0000-0002-0061-7372", "researcher": {"href": "https://publications.scilifelab.se/researcher/12af3cfa4f55436ea4fc7d64c378229e.json"}}, {"family": "Hewitt", "given": "Graeme", "initials": "G"}, {"family": "Boulton", "given": "Simon J", "initials": "SJ"}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal article", "published": "2021-09-06", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "10", "issn-l": "2050-084X"}, "abstract": "The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks.", "doi": "10.7554/eLife.71420", "pmid": "34486521", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "71420"}, {"db": "pmc", "key": "PMC8463071"}], "notes": [], "created": "2021-11-03T13:44:23.365Z", "modified": "2021-12-10T13:27:15.631Z"}, {"entity": "publication", "iuid": "6878fad3e80b4b2d84ef0cf49160ba6b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6878fad3e80b4b2d84ef0cf49160ba6b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6878fad3e80b4b2d84ef0cf49160ba6b"}}, "title": "Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch.", "authors": [{"family": "Lehmann", "given": "Laura C", "initials": "LC", "orcid": "0000-0003-2518-5606", "researcher": {"href": "https://publications.scilifelab.se/researcher/e73ae6d30ebe4c68971f3b0908d061c6.json"}}, {"family": "Bacic", "given": "Luka", "initials": "L", "orcid": "0000-0001-6896-3506", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bcd56cafd294116870c894ba344cf12.json"}}, {"family": "Hewitt", "given": "Graeme", "initials": "G"}, {"family": "Brackmann", "given": "Klaus", "initials": "K"}, {"family": "Sabantsev", "given": "Anton", "initials": "A", "orcid": "0000-0002-8559-8894", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae73150df15e4730be688fc5137a1389.json"}}, {"family": "Gaullier", "given": "Guillaume", "initials": "G", "orcid": "0000-0003-3405-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/26bde2020c164cff8216338fb2d6d652.json"}}, {"family": "Pytharopoulou", "given": "Sofia", "initials": "S"}, {"family": "Degliesposti", "given": "Gianluca", "initials": "G"}, {"family": "Okkenhaug", "given": "Hanneke", "initials": "H"}, {"family": "Tan", "given": "Song", "initials": "S"}, {"family": "Costa", "given": "Alessandro", "initials": "A"}, {"family": "Skehel", "given": "J Mark", "initials": "JM"}, {"family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-6936-6834", "researcher": {"href": "https://publications.scilifelab.se/researcher/8be210bb12b54a19b4020803fa0c3357.json"}}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal article", "published": "2020-12-22", "journal": {"title": "Cell Rep", "issn": "2211-1247", "issn-l": null, "volume": "33", "issue": "12", "pages": "108529"}, "abstract": "Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.", "doi": "10.1016/j.celrep.2020.108529", "pmid": "33357431", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)31518-7"}, {"db": "pmc", "key": "PMC7116876"}, {"db": "mid", "key": "EMS117809"}], "notes": [], "created": "2021-03-16T07:24:16.174Z", "modified": "2023-12-04T10:15:55.187Z"}, {"entity": "publication", "iuid": "eafab88fefb94d66b47cebbd0ea62bd2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eafab88fefb94d66b47cebbd0ea62bd2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eafab88fefb94d66b47cebbd0ea62bd2"}}, "title": "Mechanistic Insights into Autoinhibition of the Oncogenic Chromatin Remodeler ALC1", "authors": [{"family": "Lehmann", "given": "Laura C", "initials": "LC", "orcid": "0000-0003-2518-5606", "researcher": {"href": "https://publications.scilifelab.se/researcher/e73ae6d30ebe4c68971f3b0908d061c6.json"}}, {"family": "Hewitt", "given": "Graeme", "initials": "G"}, {"family": "Aibara", "given": "Shintaro", "initials": "S", "orcid": "0000-0003-2221-482X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d66746c4bec5414da78b2a325a13328f.json"}}, {"family": "Leitner", "given": "Alexander", "initials": "A"}, {"family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "researcher": {"href": "https://publications.scilifelab.se/researcher/67842d62534d4612a5e92f7a275df4dc.json"}}, {"family": "Maslen", "given": "Sarah L", "initials": "SL"}, {"family": "Maturi", "given": "Varun", "initials": "V", "orcid": "0000-0003-1177-0839", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bd84539b66b4e79964ec0330f1aefd7.json"}}, {"family": "Chen", "given": "Yang", "initials": "Y"}, {"family": "van der Spoel", "given": "David", "initials": "D", "orcid": "0000-0002-7659-8526", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf896790b2f844f181e60f3b01d7ae0f.json"}}, {"family": "Skehel", "given": "J Mark", "initials": "JM"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c1626d991f3485e81232db174537e6d.json"}}, {"family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-6936-6834", "researcher": {"href": "https://publications.scilifelab.se/researcher/8be210bb12b54a19b4020803fa0c3357.json"}}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal-article", "published": "2017-12-00", "journal": {"volume": "68", "issn": "1097-2765", "issue": "5", "pages": "847-859.e7", "title": "Molecular Cell", "issn-l": "1097-2765"}, "abstract": "Human ALC1 is an oncogene-encoded chromatin-remodeling enzyme required for DNA repair that possesses a poly(ADP-ribose) (PAR)-binding macro domain. Its engagement with PARylated PARP1 activates ALC1 at sites of DNA damage, but the underlying mechanism remains unclear. Here, we establish a dual role for the macro domain in autoinhibition of ALC1 ATPase activity and coupling to nucleosome mobilization. In the absence of DNA damage, an inactive conformation of the ATPase is maintained by juxtaposition of the macro domain against predominantly the C-terminal ATPase lobe through conserved electrostatic interactions. Mutations within this interface displace the macro domain, constitutively activate the ALC1 ATPase independent of PARylated PARP1, and alter the dynamics of ALC1 recruitment at DNA damage sites. Upon DNA damage, binding of PARylated PARP1 by the macro domain induces a conformational change that relieves autoinhibitory interactions with the ATPase motor, which selectively activates ALC1 remodeling upon recruitment to sites of DNA damage.", "doi": "10.1016/j.molcel.2017.10.017", "pmid": "29220652", "labels": {"Protein Science Facility (PSF)": "Service", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5745148"}, {"db": "pii", "key": "S1097-2765(17)30792-X"}], "notes": [], "created": "2018-04-11T08:26:47.042Z", "modified": "2023-12-04T10:12:26.534Z"}]}