title: hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity.
abstract: Prim-pol is a recently identified DNA primase-polymerase belonging to the archaeao-eukaryotic primase (AEP) superfamily. Here, we characterize a previously unrecognized prim-pol in human cells, which we designate hPrimpol1 (human primase-polymerase 1). hPrimpol1 possesses primase and DNA polymerase activities in vitro, interacts directly with RPA1 and is recruited to sites of DNA damage and stalled replication forks in an RPA1-dependent manner. Cells depleted of hPrimpol1 display increased spontaneous DNA damage and defects in the restart of stalled replication forks. Both RPA1 binding and the primase activity of hPrimpol1 are required for its cellular function during DNA replication. Our results indicate that hPrimpol1 is a novel factor involved in the response to DNA replication stress.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.forename: Jiangman
authors.initials: J
authors.lastname: Lou
authors.forename: Yisui
authors.initials: Y
authors.lastname: Xia
authors.forename: Bei
authors.initials: B
authors.lastname: Su
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Jiamin
authors.initials: J
authors.lastname: Cui
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sun
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Lou
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D019915:DNA Primase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015894:Genome, Human; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051716:Replication Protein A / Q000378:metabolism
chemical_list: D064251:Multifunctional Enzymes; C497167:RPA1 protein, human; D051716:Replication Protein A; D004247:DNA; D019915:DNA Primase; C585901:PrimPol protein, human; D004259:DNA-Directed DNA Polymerase