title: Okazaki fragment metabolism.
abstract: Cellular DNA replication requires efficient copying of the double-stranded chromosomal DNA. The leading strand is elongated continuously in the direction of fork opening, whereas the lagging strand is made discontinuously in the opposite direction. The lagging strand needs to be processed to form a functional DNA segment. Genetic analyses and reconstitution experiments identified proteins and multiple pathways responsible for maturation of the lagging strand. In both prokaryotes and eukaryotes the lagging-strand fragments are initiated by RNA primers, which are removed by a joining mechanism involving strand displacement of the primer into a flap, flap removal, and then ligation. Although the prokaryotic fragments are ~1200 nucleotides long, the eukaryotic fragments are much shorter, with lengths determined by nucleosome periodicity. The prokaryotic joining mechanism is simple and efficient. The eukaryotic maturation mechanism involves many enzymes, possibly three pathways, and regulation that can shift from high efficiency to high fidelity.
authors: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors: Lata
authors: L
authors: Balakrishnan
authors: Robert A
authors: RA
authors: Bambara
mesh_terms: D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology*; D005057:Eukaryotic Cells / Q000201:enzymology / Q000378:metabolism; D019143:Evolution, Molecular; D008957:Models, Genetic; D011387:Prokaryotic Cells / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: C022262:Okazaki fragments; D004247:DNA
references: J Bacteriol. 1993 Oct;175(20):6731-4
references: 8407851
references: Proc Natl Acad Sci U S A. 1990 Feb;87(3):1023-7
references: 1967833
references: Mol Cell Biol. 1997 Apr;17(4):2136-42
references: 9121462
references: J Biol Chem. 2009 May 29;284(22):15158-72
references: 19329425
references: Nature. 2009 Dec 17;462(7275):940-3
references: 19924126
references: J Biol Chem. 1998 Dec 4;273(49):33064-72
references: 9830061
references: Methods Cell Biol. 1973;7:361-462
references: 4592524
references: Annu Rev Biochem. 1998;67:721-51
references: 9759502
references: Nucleic Acids Res. 2004 Aug 09;32(14):4205-16
references: 15302919
references: Biochemistry. 1993 Mar 30;32(12):3027-37
references: 7681326
references: Chem Rev. 2006 Feb;106(2):453-73
references: 16464014
references: Curr Biol. 2006 Jan 24;16(2):202-7
references: 16431373
references: Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):115-28
references: 15814431
references: J Biol Chem. 1993 Dec 15;268(35):26179-89
references: 8253737
references: Biochemistry. 2012 Jan 10;51(1):416-24
references: 22148433
references: Mol Cell. 2001 Jun;7(6):1221-31
references: 11430825
references: Mol Cell Biol. 1999 Dec;19(12):8361-71
references: 10567561
references: J Biol Chem. 2011 Mar 4;286(9):6865-70
references: 21177245
references: J Biol Chem. 2010 Dec 31;285(53):41712-23
references: 20959454
references: Mol Cell. 2012 Aug 10;47(3):444-56
references: 22749529
references: Nature. 2001 Jul 26;412(6845):456-61
references: 11473323
references: J Biol Chem. 1994 Apr 8;269(14):10923-34
references: 8144677
references: J Biol Chem. 1992 Jul 15;267(20):14129-37
references: 1321135
references: J Mol Biol. 1990 Dec 5;216(3):475-9
references: 2258921
references: J Biol Chem. 1995 Dec 22;270(51):30377-83
references: 8530463
references: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7642-6
references: 7644470
references: Cell Cycle. 2005 Feb;4(2):221-4
references: 15655350
references: J Biol Chem. 2002 Feb 8;277(6):3894-901
references: 11711545
references: Biochim Biophys Acta. 2010 May;1804(5):1180-9
references: 19540940
references: Nat Struct Mol Biol. 2011 Aug 14;18(9):1015-9
references: 21841787
references: J Biol Chem. 2010 Nov 5;285(45):34922-31
references: 20739288
references: Proc Natl Acad Sci U S A. 1968 Feb;59(2):598-605
references: 4967086
references: J Biol Chem. 2010 Feb 12;285(7):4398-404
references: 20019387
references: J Biol Chem. 1992 Jan 5;267(1):462-6
references: 1309747
references: Crit Rev Biochem Mol Biol. 2010 Apr;45(2):71-96
references: 20131965
references: Mol Cell. 2005 Jul 1;19(1):123-33
references: 15989970
references: J Biol Chem. 2006 Sep 8;281(36):26051-61
references: 16837458
references: Science. 2009 Aug 14;325(5942):834-40
references: 19608861
references: Mol Cell. 2008 Nov 7;32(3):325-36
references: 18995831
references: Biochim Biophys Acta. 1966 Dec 21;129(3):651-4
references: 5337977
references: Cell. 2011 Apr 15;145(2):198-211
references: 21496641
references: Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9803-7
references: 7524089
references: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9924-9
references: 12119409
references: J Biol Chem. 2008 Nov 14;283(46):31356-65
references: 18799459
references: J Biol Chem. 1985 Sep 5;260(19):10840-6
references: 3161883
references: Annu Rev Biochem. 1997;66:61-92
references: 9242902
references: Cell Cycle. 2011 May 15;10(10):1690-8
references: 21508669
references: EMBO J. 2006 May 17;25(10):2199-208
references: 16642036
references: J Biol Chem. 2004 May 7;279(19):20194-9
references: 14988403
references: J Biol Chem. 2010 Sep 10;285(37):28496-505
references: 20628185
references: FEBS J. 2009 Mar;276(6):1494-505
references: 19228196
references: Annu Rev Biochem. 1980;49:421-57
references: 6250445
references: Cell. 1999 Jan 8;96(1):153-63
references: 9989506
references: Science. 2007 Jul 6;317(5834):127-30
references: 17615360
references: Cold Spring Harb Symp Quant Biol. 1983;47 Pt 2:655-68
references: 6305581
references: J Biol Chem. 2009 Feb 13;284(7):4041-5
references: 18835809
references: Cell Cycle. 2011 Aug 15;10(16):2620-1
references: 21829100
references: J Biol Chem. 2003 Jan 17;278(3):1618-25
references: 12424238
references: J Biol Chem. 1992 Apr 15;267(11):7284-94
references: 1348504
references: Nature. 2012 Mar 14;483(7390):434-8
references: 22419157
references: Nat Cell Biol. 2006 Dec;8(12):1359-68
references: 17115032
references: J Biol Chem. 1997 Feb 21;272(8):4647-50
references: 9081985
references: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2244-9
references: 9482870
references: Crit Rev Biochem Mol Biol. 2003;38(5):433-52
references: 14693726
references: Nucleic Acids Res. 2010 Jan;38(3):920-30
references: 19934252
references: Annu Rev Biochem. 2002;71:133-63
references: 12045093
references: Bioessays. 1997 Mar;19(3):233-40
references: 9080773
references: PLoS Genet. 2005 Dec;1(6):e61
references: 16327883
references: J Mol Cell Biol. 2011 Feb;3(1):23-30
references: 21278448
references: Biochemistry. 1994 Mar 1;33(8):2247-54
references: 8117681
references: Mol Cell Biol. 2006 Apr;26(7):2490-500
references: 16537895
references: Nature. 1990 Aug 9;346(6284):534-9
references: 2165567