title: The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch.
abstract: Emerging evidence suggests that Cdc13-Stn1-Ten1 (CST), an RPA-like ssDNA-binding complex, may regulate primase-Pol α (PP) activity at telomeres constitutively, and at other genomic locations under conditions of replication stress. Here we examine the mechanisms of PP stimulation by CST using purified complexes derived from Candida glabrata. While CST does not enhance isolated DNA polymerase activity, it substantially augments both primase activity and primase-to-polymerase switching. CST also simultaneously shortens the RNA and lengthens the DNA in the chimeric products. Stn1, the most conserved subunit of CST, is alone capable of PP stimulation. Both the N-terminal OB fold and the C-terminal winged-helix domains of Stn1 can bind to the Pol12 subunit of the PP complex and stimulate PP activity. Our findings provide mechanistic insights on a well-conserved pathway of PP regulation that is critical for genome stability.
authors.affiliation: W. R. Hearst Microbiology Research Center, Department of Microbiology &Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors.forename: Neal F
authors.initials: NF
authors.lastname: Lue
authors.affiliation: W. R. Hearst Microbiology Research Center, Department of Microbiology &Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Chan
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Jerard
authors.initials: J
authors.lastname: Hurwitz
mesh_terms: D001665:Binding Sites; D041221:Candida glabrata / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D019915:DNA Primase / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D005656:Fungal Proteins; D012331:RNA, Fungal; D034501:Telomere-Binding Proteins; D019915:DNA Primase; D004256:DNA Polymerase I