title: PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).
abstract: PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal that PARP3 employs a conserved DNA-binding interface to detect and stably bind DNA breaks and to accumulate at sites of chromosome damage. PARP3 preferentially binds to and is activated by mononucleosomes containing nicked DNA and which target PARP3 trans-ribosylation activity to a single-histone substrate. Although nicks in naked DNA stimulate PARP3 autoribosylation, nicks in mononucleosomes promote the trans-ribosylation of histone H2B specifically at Glu2. These data identify PARP3 as a molecular sensor of nicked nucleosomes and demonstrate, for the first time, the ribosylation of chromatin at a site-specific DNA single-strand break.
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Gabrielle J
authors.initials: GJ
authors.lastname: Grundy
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Polo
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Rulten
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.|CAPES Foundation, Ministry of Education of Brazil, Brasilia/DF 70040-020, Brazil.
authors.forename: Nicolas C
authors.initials: NC
authors.lastname: Hoch
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Pathompong
authors.initials: P
authors.lastname: Paomephan
authors.affiliation: Cross-faculty NMR centre, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Sweet
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, St Michael's Building, Portsmouth PO1 2DT, UK.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thorne
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Antony W
authors.identifier: 0000-0002-2912-8273
authors.initials: AW
authors.lastname: Oliver
authors.affiliation: Cross-faculty NMR centre, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Matthews
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Laurence H
authors.identifier: 0000-0002-6910-1809
authors.initials: LH
authors.lastname: Pearl
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Caldecott
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D012266:Ribose / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012266:Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases