{"entity": "publication", "iuid": "002242ae64214f1db1e2df2ad40c6895", "timestamp": "2026-08-29T04:16:47.592Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/002242ae64214f1db1e2df2ad40c6895.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/002242ae64214f1db1e2df2ad40c6895"}}, "title": "Restriction of AID activity and somatic hypermutation by PARP-1.", "authors": [{"family": "Tepper", "given": "Sandra", "initials": "S"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O"}, {"family": "Cz\u0142onka", "given": "Ewelina", "initials": "E"}, {"family": "Bello", "given": "Amanda", "initials": "A"}, {"family": "Schmidt", "given": "Angelika", "initials": "A"}, {"family": "Jeschke", "given": "Julia", "initials": "J"}, {"family": "Fischbach", "given": "Arthur", "initials": "A"}, {"family": "Pfeil", "given": "Ines", "initials": "I"}, {"family": "Petersen-Mahrt", "given": "Svend K", "initials": "SK"}, {"family": "Mangerich", "given": "Aswin", "initials": "A"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Leonhardt", "given": "Heinrich", "initials": "H"}, {"family": "Jungnickel", "given": "Berit", "initials": "B"}], "type": "journal article", "published": "2019-08-22", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "47", "issue": "14", "pages": "7418-7429", "issn-l": "0305-1048"}, "abstract": "Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification.", "doi": "10.1093/nar/gkz466", "pmid": "31127309", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6698665"}, {"db": "pii", "key": "5498626"}], "notes": [], "created": "2026-08-20T09:50:37.182Z", "modified": "2026-08-20T09:50:37.193Z"}