title: A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress.
abstract: Genomic instability, a major hallmark of cancer cells, is caused by incorrect or ineffective DNA repair. Many DNA repair mechanisms cooperate in cells to fight DNA damage, and are generally regulated by post-translational modification of key factors. Poly-ADP-ribosylation, catalyzed by PARP1, is a post-translational modification playing a prominent role in DNA repair, but much less is known about mono-ADP-ribosylation. Here we report that mono-ADP-ribosylation plays an important role in homologous recombination DNA repair, a mechanism essential for replication fork stability and double strand break repair. We show that the mono-ADP-ribosyltransferase PARP14 interacts with the DNA replication machinery component PCNA and promotes replication of DNA lesions and common fragile sites. PARP14 depletion results in reduced homologous recombination, persistent RAD51 foci, hypersensitivity to DNA damaging agents and accumulation of DNA strand breaks. Our work uncovered PARP14 as a novel factor required for mitigating replication stress and promoting genomic stability.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Nicolae
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Aho
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Choe
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Constantin
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA Suzhou Health College, Suzhou, Jiangsu 215009, P.R. China.
authors.forename: He-Juan
authors.initials: HJ
authors.lastname: Hu
authors.affiliation: Genome Instability Section, National Human Genome Research Institute, Bethesda, MD 20892, USA.
authors.forename: Deokjae
authors.initials: D
authors.lastname: Lee
authors.affiliation: Genome Instability Section, National Human Genome Research Institute, Bethesda, MD 20892, USA.
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA gmoldovan@hmc.psu.edu.
authors.forename: George-Lucian
authors.initials: GL
authors.lastname: Moldovan
mesh_terms: D002460:Cell Line; D043283:Chromosome Fragile Sites; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; C584083:PARP14 protein, human; D011065:Poly(ADP-ribose) Polymerases