title: Low rate of replication fork progression lengthens the replication timing of a locus containing an early firing origin.
abstract: Invariance of temporal order of genome replication in eukaryotic cells and its correlation with gene activity has been well-documented. However, recent data suggest a relax control of replication timing. To evaluate replication schedule accuracy, we detailed the replicational organization of the developmentally regulated php locus that we previously found to be lately replicated, even though php gene is highly transcribed in naturally synchronous plasmodia of Physarum. Unexpectedly, bi-dimensional agarose gel electrophoreses of DNA samples prepared at specific time points of S phase showed that replication of the locus actually begins at the onset of S phase but it proceeds through the first half of S phase, so that complete replication of php-containing DNA fragments occurs in late S phase. Origin mapping located replication initiation upstream php coding region. This proximity and rapid fork progression through the coding region result in an early replication of php gene. We demonstrated that afterwards an unusually low fork rate and unidirectional fork pausing prolong complete replication of php locus, and we excluded random replication timing. Importantly, we evidenced that the origin linked to php gene in plasmodium is not fired in amoebae when php expression dramatically reduced, further illustrating replication-transcription coupling in Physarum.
authors: CNRS-FRE 2937, Institut André Lwoff, BP8, 94800 Villejuif, France. benard@vjf.cnrs.fr
authors: Marianne
authors: M
authors: Bénard
authors: Chrystelle
authors: C
authors: Maric
authors: Gérard
authors: G
authors: Pierron
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000187:drug effects; D042522:DNA Replication Timing; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006918:Hydroxyurea / Q000494:pharmacology; D016839:Physarum polycephalum / Q000235:genetics* / Q000254:growth & development; D011401:Promoter Regions, Genetic; D018741:Replication Origin; D016196:S Phase / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D006918:Hydroxyurea
references: Mol Cell Biol. 1992 Oct;12(10):4305-13
references: 1406623
references: Mol Cell Biol. 1993 Jan;13(1):449-61
references: 8093328
references: Nucleic Acids Res. 1999 May 15;27(10):2091-8
references: 10219081
references: Methods Enzymol. 1995;262:613-27
references: 8594382
references: Proc Natl Acad Sci U S A. 1965 May;53(5):924-31
references: 5222560
references: J Cell Biol. 1998 Mar 23;140(6):1285-95
references: 9508763
references: Proc Natl Acad Sci U S A. 1973 Dec;70(12):3395-9
references: 4128545
references: Cell. 1988 Nov 18;55(4):637-43
references: 3052854
references: Science. 2001 Oct 5;294(5540):115-21
references: 11588253
references: Nucleic Acids Res. 1992 Jul 11;20(13):3309-15
references: 1630902
references: Mol Cell. 2001 May;7(5):971-80
references: 11389844
references: Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5
references: 6326095
references: Trends Genet. 2005 Aug;21(8):444-9
references: 15951049
references: Cell. 1987 Nov 6;51(3):463-71
references: 2822257
references: Hum Mol Genet. 2004 Jan 15;13(2):191-202
references: 14645202
references: Nat Rev Genet. 2001 Aug;2(8):640-5
references: 11483989
references: Proc Natl Acad Sci U S A. 2005 May 3;102(18):6419-24
references: 15845769
references: Bioessays. 2003 Feb;25(2):116-25
references: 12539237
references: Exp Cell Res. 1990 Feb;186(2):299-305
references: 1967581
references: Mol Cell. 2003 Dec;12(6):1525-36
references: 14690605
references: Biochim Biophys Acta. 1966 Jan 18;114(1):108-15
references: 5936951
references: Cell. 1978 Dec;15(4):1519-26
references: 729005
references: Biochim Biophys Acta. 1969 Jan 21;174(1):246-52
references: 4237205
references: Exp Cell Res. 1992 Aug;201(2):506-13
references: 1353456
references: Trends Cell Biol. 1993 May;3(5):161-7
references: 14731611
references: Nat Cell Biol. 2006 Dec;8(12):1313-6
references: 17139278
references: Methods Mol Biol. 2004;277:19-28
references: 15201446
references: Nat Genet. 2002 Nov;32(3):438-42
references: 12355067
references: EMBO Rep. 2006 Aug;7(8):812-6
references: 16845368
references: Nucleic Acids Res. 1998 May 1;26(9):2042-49
references: 9547257
references: Curr Opin Cell Biol. 2002 Jun;14(3):377-83
references: 12067662
references: Genes Dev. 2004 Dec 15;18(24):3094-105
references: 15601823
references: EMBO Rep. 2003 May;4(5):474-8
references: 12776736
references: Science. 1995 Nov 10;270(5238):994-7
references: 7481806
references: Nucleic Acids Res. 1989 Jan 25;17(2):553-66
references: 2915922
references: Genes Dev. 2002 Jun 1;16(11):1383-96
references: 12050116
references: J Cell Sci. 1980 Feb;41:105-13
references: 7364877
references: Genes Dev. 2004 Feb 15;18(4):397-410
references: 14977920
references: Eur J Cell Biol. 1982 Nov;29(1):104-13
references: 6217973
references: Mol Cell Biol. 1996 Mar;16(3):968-76
references: 8622700
references: Mol Biol Cell. 2006 Jan;17(1):308-16
references: 16251353
references: Am J Hum Genet. 1987 Feb;40(2):151-73
references: 3551593
references: Mol Biol Cell. 1992 Sep;3(9):999-1013
references: 1330093
references: Nat Cell Biol. 2006 Feb;8(2):148-55
references: 16429127
references: Nat Rev Mol Cell Biol. 2003 Jan;4(1):25-32
references: 12511866
references: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17771-6
references: 15591350
references: Nucleic Acids Res. 1995 May 11;23(9):1447-53
references: 7784195
references: Nucleic Acids Res. 2002 Jun 1;30(11):2261-9
references: 12034812
references: Mol Biol Cell. 2006 Dec;17(12):5337-45
references: 17005913
references: Mol Cell. 2005 Nov 23;20(4):575-87
references: 16307921
references: Biochemistry. 1979 Nov 27;18(24):5294-9
references: 518835