{"entity": "researcher", "timestamp": "2026-07-20T21:47:51.147Z", "family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-6936-6834", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/8be210bb12b54a19b4020803fa0c3357.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/8be210bb12b54a19b4020803fa0c3357"}}, "publications": [{"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"}]}