title: Processing of lagging-strand intermediates in vitro by herpes simplex virus type 1 DNA polymerase.
abstract: The processing of lagging-strand intermediates has not been demonstrated in vitro for herpes simplex virus type 1 (HSV-1). Human flap endonuclease-1 (Fen-1) was examined for its ability to produce ligatable products with model lagging-strand intermediates in the presence of the wild-type or exonuclease-deficient (exo(-)) HSV-1 DNA polymerase (pol). Primer/templates were composed of a minicircle single-stranded DNA template annealed to primers that contained 5' DNA flaps or 5' annealed DNA or RNA sequences. Gapped DNA primer/templates were extended but not significantly strand displaced by the wild-type HSV-1 pol, although significant strand displacement was observed with exo(-) HSV-1 pol. Nevertheless, the incubation of primer/templates containing 5' flaps with either wild-type or exo(-) HSV-1 pol and Fen-1 led to the efficient production of nicks that could be sealed with DNA ligase I. Both polymerases stimulated the nick translation activity of Fen-1 on DNA- or RNA-containing primer/templates, indicating that the activities were coordinated. Further evidence for Fen-1 involvement in HSV-1 DNA synthesis is suggested by the ability of a transiently expressed green fluorescent protein fusion with Fen-1 to accumulate in viral DNA replication compartments in infected cells and by the ability of endogenous Fen-1 to coimmunoprecipitate with an essential viral DNA replication protein in HSV-1-infected cells.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zetang
authors.initials: Z
authors.lastname: Wu
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Cardoso
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Parris
mesh_terms: D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D045585:Flap Endonucleases / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; D045585:Flap Endonucleases; C043417:DNA polymerase, Simplexvirus; C468317:FEN1 protein, human
references.citation: Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):115-28
references.pmid: 15814431
references.citation: J Biol Chem. 1991 Mar 5;266(7):4484-8
references.pmid: 1847923
references.citation: J Virol. 1996 Mar;70(3):1751-8
references.pmid: 8627697
references.citation: J Biol Chem. 1999 Oct 1;274(40):28059-62
references.pmid: 10497152
references.citation: Genes Dev. 2004 Nov 15;18(22):2764-73
references.pmid: 15520275
references.citation: Genome Biol. 2002;3(4):REVIEWS3005
references.pmid: 11983065
references.citation: J Virol. 1983 Dec;48(3):591-603
references.pmid: 6313961
references.citation: J Virol. 1977 Aug;23(2):394-411
references.pmid: 196115
references.citation: Annu Rev Biochem. 1998;67:721-51
references.pmid: 9759502
references.citation: J Gen Virol. 1989 Sep;70 ( Pt 9):2357-64
references.pmid: 2476527
references.citation: J Virol. 1990 Dec;64(12):5738-49
references.pmid: 2173766
references.citation: J Virol. 2004 Jun;78(11):5856-66
references.pmid: 15140983
references.citation: J Virol. 1993 Oct;67(10):5922-31
references.pmid: 8396660
references.citation: Eur J Biochem. 1979 Jul;98(1):231-44
references.pmid: 223846
references.citation: Prog Nucleic Acid Res Mol Biol. 2001;70:77-118
references.pmid: 11642367
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3896-900
references.pmid: 10760262
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12863-8
references.pmid: 9371766
references.citation: J Biol Chem. 2000 Apr 7;275(14):10498-505
references.pmid: 10744741
references.citation: Mol Cell Biol. 2007 Apr;27(8):3176-86
references.pmid: 17283043
references.citation: J Biol Chem. 2008 Dec 5;283(49):34129-40
references.pmid: 18927077
references.citation: J Cell Biol. 1997 Nov 3;139(3):579-87
references.pmid: 9348276
references.citation: J Biol Chem. 1994 Apr 8;269(14):10923-34
references.pmid: 8144677
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7487-92
references.pmid: 9207118
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5122-7
references.pmid: 11309502
references.citation: J Virol. 2004 May;78(9):4783-96
references.pmid: 15078960
references.citation: J Virol. 1994 Jun;68(6):3693-701
references.pmid: 8189507
references.citation: J Biol Chem. 2002 Jun 21;277(25):22361-9
references.pmid: 11948189
references.citation: J Biol Chem. 2001 Jul 6;276(27):24817-25
references.pmid: 11331287
references.citation: J Biol Chem. 1978 May 25;253(10):3557-62
references.pmid: 206546
references.citation: Virology. 1974 Sep;61(1):87-99
references.pmid: 4370347
references.citation: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1105-9
references.pmid: 1847509
references.citation: Curr Genet. 1998 Jul;34(1):21-9
references.pmid: 9683672
references.citation: J Biol Chem. 1995 Jun 9;270(23):14148-53
references.pmid: 7775476
references.citation: Cell. 1988 Dec 2;55(5):857-68
references.pmid: 2847874
references.citation: J Biol Chem. 2007 Apr 13;282(15):10865-72
references.pmid: 17296606
references.citation: J Biol Chem. 2006 Sep 8;281(36):26051-61
references.pmid: 16837458
references.citation: J Biol Chem. 2003 Jan 17;278(3):1626-33
references.pmid: 12424237
references.citation: J Virol. 2002 Oct;76(20):10270-81
references.pmid: 12239303
references.citation: IUBMB Life. 2003 Jan;55(1):13-22
references.pmid: 12716057
references.citation: J Biol Chem. 1995 Sep 22;270(38):22109-12
references.pmid: 7673186
references.citation: J Biol Chem. 1996 Nov 15;271(46):29245-54
references.pmid: 8910584
references.citation: J Biol Chem. 2004 Apr 30;279(18):18535-43
references.pmid: 14982924
references.citation: J Biol Chem. 2009 Feb 13;284(7):4041-5
references.pmid: 18835809
references.citation: J Virol. 2003 Dec;77(23):12646-59
references.pmid: 14610187
references.citation: J Virol. 2003 Sep;77(18):10147-53
references.pmid: 12941927
references.citation: J Virol. 1989 Jan;63(1):196-204
references.pmid: 2535726
references.citation: J Biol Chem. 2003 Jan 17;278(3):1618-25
references.pmid: 12424238
references.citation: Mol Cell. 2002 Dec;10(6):1355-65
references.pmid: 12504011
references.citation: J Cell Sci. 2002 Apr 1;115(Pt 7):1551-61
references.pmid: 11896201
references.citation: J Virol. 1997 Mar;71(3):2390-9
references.pmid: 9032376
references.citation: Curr Biol. 2000 Jul 27-Aug 10;10(15):919-22
references.pmid: 10959839
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14298-303
references.pmid: 11724925
references.citation: Crit Rev Biochem Mol Biol. 2003;38(5):433-52
references.pmid: 14693726
references.citation: Annu Rev Biochem. 2004;73:589-615
references.pmid: 15189154
references.citation: J Biol Chem. 2000 Dec 1;275(48):38022-31
references.pmid: 10984490
references.citation: J Biol Chem. 1993 Jul 15;268(20):15136-41
references.pmid: 8392066
references.citation: J Virol. 1996 Mar;70(3):1759-67
references.pmid: 8627698
references.citation: Biochemistry. 1992 Dec 1;31(47):11762-71
references.pmid: 1445910
references.citation: Mutat Res. 2000 Aug 30;460(3-4):301-18
references.pmid: 10946235
references.citation: J Biol Chem. 2003 Mar 14;278(11):8996-9004
references.pmid: 12519753
references.citation: Nucleic Acids Res. 2005 Jun 21;33(11):3521-8
references.pmid: 15972794
references.citation: Nature. 1991 Jan 31;349(6308):429-31
references.pmid: 1671528