{"entity": "publication", "iuid": "a537001d14d34f14b3048bdf35e0b950", "timestamp": "2026-07-22T14:37:32.481Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a537001d14d34f14b3048bdf35e0b950.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a537001d14d34f14b3048bdf35e0b950"}}, "title": "Mechanistic insights into PCBP1-driven unfolding of selected i-motif DNA at G1/S checkpoint.", "authors": [{"family": "Sengupta", "given": "Pallabi", "initials": "P", "orcid": "0000-0002-1413-9412", "researcher": {"href": "https://publications.scilifelab.se/researcher/851c95f648f242e0ba67202279725796.json"}}, {"family": "Gillet", "given": "Natacha", "initials": "N", "orcid": "0000-0002-7657-6861", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce5b43ffd5e44fbe926a3d26064b6760.json"}}, {"family": "Obi", "given": "Ikenna", "initials": "I", "orcid": "0000-0003-0364-8964", "researcher": {"href": "https://publications.scilifelab.se/researcher/e46c65e7b0e540b0a7c225d54c1502d7.json"}}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}], "type": "journal article", "published": "2026-02-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "pages": "1149", "issn-l": "2041-1723"}, "abstract": "I-motifs are non-canonical, four-stranded DNA structures in cytosine-rich genomic regions, yet their protein-mediated regulation remains underexplored. Here, we identify PCBP1 (Poly(rC)-binding protein 1) as a selective i-motif-binding protein that unfolds specific i-motifs depending on their protonation and hairpin-forming propensities. Systematic truncation reveals that individual K-homology (KH) domains of PCBP1 cannot selectively bind or unfold i-motifs, but their coordinated actions restore wild-type PCBP1 functions. Using biochemical, biophysical, and molecular dynamics studies, we demonstrate that KH1+2 domains remodel i-motifs, recruiting KH3 to facilitate unfolding and efficient DNA replication. Chromatin and cell-based investigations reveal that PCBP1-knockdown increases i-motif formation at specific genomic loci, coinciding with G1/S arrest and elevated \u03b3H2AX, indicative of genomic instability. During G1/S transition, PCBP1 occupancy peaks at these i-motif loci, ensuring i-motif resolution in early S phase. These findings establish PCBP1 as a critical regulator of i-motif dynamics, directly linking its unfolding activity to G1/S transition and genome stability.", "doi": "10.1038/s41467-026-68822-5", "pmid": "41629296", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-026-68822-5"}, {"db": "pmc", "key": "PMC12865031"}], "notes": [], "created": "2026-02-04T15:32:08.919Z", "modified": "2026-02-04T15:32:09.419Z"}