{"entity": "researcher", "timestamp": "2026-07-20T22:02:20.941Z", "family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "affiliations": ["Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Box 596, 75124, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/67842d62534d4612a5e92f7a275df4dc.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/67842d62534d4612a5e92f7a275df4dc"}}, "publications": [{"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": "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"}]}