Nuclear Structure and Function Research Group

Resources for CHAPTER 3: REPLICATION
Updated on 20 October, 2016

Principles
        Box 3-1. Bacterial DNA polymerases
    Tracking versus immobile DNA polymerases
Replication factories
The mechanics of synthesis at the fork
    Separating parental strands
        Box 3-2. Topoisomerases and anti-cancer drugs
    RNA primers
    The asymmetric fork
    Proofreading
    Replicating chromatin
The initiation of synthesis
        Box 3-3. The origin of replication of E. coli
    Simple origins of SV40 virus and yeast
        Box 3-4. Two methods for mapping origins
    Complex mammalian origins
    Role of transcription during initiation
Replicating ends
        Box 3-5. Telomerase in ageing and cancer

Principles
Figure: 3-1, 3-2, 3-3.
Additional reference:
Berdis, A.J. (2009). Mechanisms of DNA polymerases. Chem. Rev. 109, 2862-2879. [PubMed]
Foti, J.J., and Walker, G.C. (2010). SnapShot: DNA polymerases II mammals. Cell 141, 370. [PubMed]
Hanawalt, P.C. (2004).  Density matters: the semiconservative replication of DNA.  Proc. Natl. Acad. Sci. USA 101, 17889-17894.  [PubMed]
Loeb, L.A., and Monnat R.J. (2008). DNA polymerases and human disease. Nat. Rev. Genet. 9, 594-604. [PubMed]
Méndez, J. and Stillman, B. (2003).  Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins.  BioEssays 25, 1158-1167.  [PubMed]
Steitz, T.A. (2006). Visualizing polynucleotide polymerase machines at work. EMBO J. 25, 3458-3468. [PubMed]
Web link:
http://www.accessexcellence.com/AB/GG/ The basics from the National Health Museum, USA.

Box 3-1. Bacterial DNA polymerases
Reference:
Baker, T.J. and Wickner, S.H. (1992). Genetics and enzymology of DNA replication in Escherichia coli. Annu. Rev. Genet. 26, 447-477.
Additional reference:
Foti, J.J., and Walker, G.C. (2010). SnapShot: DNA polymerases I prokaryotes. Cell 141, 192-192. [PubMed]
Meile, J.C., Wu, L.J., Ehrlich, S.D., Errington, J., and Noirot, P. (2006). Systematic localisation of proteins fused to the green fluorescent protein in Bacillus subtilis: identification of new proteins at the DNA replication factory. Proteomics 6, 2135-2146. [PubMed].
Yao, N.Y., and O'Donnell, M. (2008). Replisome dynamics and use of DNA trombone loops to bypass replication blocks. Mol. Biosyst. 4, 1075-1084. [PubMed]

Tracking versus immobile DNA polymerases
Figure: 3-4, 3-5, 3-6.
Reference:
Wessel, R., Schweizer, J. and Stahl, H. (1992). Simian virus 40 T-antigen DNA helicase is a hexamer which forms a binary complex during bidirectional unwinding from the viral origin of DNA replication. J. Virol. 66, 804-815. [PubMed]
Jackson, D.A. and Cook, P.R. (1986). Replication occurs at a nucleoskeleton. EMBO J. 5, 1403-1410. [PubMed]
Additional reference:
Bates, D. (2008). The bacterial replisome: back on track? Mol. Microbiol. 69, 1341-1348. [PubMed]
Fanning, E., and Zhao, K. (2009). SV40 DNA replication: from the A gene to a nanomachine. Virology 384, 352-359. [PubMed]
Gai, D., Zhao, R., Li, D., Finkielstein, C.V. and Chen, X.S. (2004).  Mechanisms of Conformational Change for a Replicative Hexameric Helicase of SV40 Large Tumor Antigen.  Cell 119, 47-60.  [PubMed]
Natsume, T., and Tanaka, T.U. (2010). Spatial regulation and organization of DNA replication within the nucleus. Chromosome Res. 18, 7-17. [PubMed]

Replication factories
Figure: 3-7, 3-8.
Reference:
Nakamura, H., Morita, T. and Sato, C. (1986). Structural organisation of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp. Cell Res. 165, 291-297. [PubMed]
Hozák, P., Hassan, A.B., Jackson, D.A. and Cook, P.R. (1993). Visualization of replication factories attached to a nucleoskeleton. Cell 73, 361-373. [PubMed]
Lemon, K.P. and Grossman, A.D. (1998). Localization of bacterial DNA polymerase: evidence for a factory model of replication. Science 282, 1516-1519. [PubMed]
Cook, P.R. (1999). The organization of replication and transcription. Science 284, 1790-1795. [PubMed]
Additional reference:
Gillespie, P.J., and Blow, J.J. (2010). Clusters, factories and domains: The complex structure of S-phase comes into focus. Cell Cycle 9, 3218-3226. [PubMed]
Lemon, K.P. and Grossman, A.D. (2000). Movement of replicating DNA through a stationary replisome. Mol. Cell 6, 1321-1330. [PubMed]
Maya-Mendoza, A., Tang, C.W., Pombo, A., and Jackson, D.A. (2009). Mechanisms regulating S phase progression in mammalian cells. Front. Biosci. 14, 4199-4213. [PubMed]
Saner, N., Karschau, J., Natsume, T., Gierlinski, M., Retkute, R., Hawkins, M., Nieduszynski, C.A., Blow, J.J., de Moura, A.P., and Tanaka, T.U. (2013). Stochastic association of neighboring replicons creates replication factories in budding yeast. J. Cell Biol. 202, 1001-1012. [PubMed]

The mechanics of synthesis at the fork
Additional reference:
Burgers, P.M. (2009). Polymerase dynamics at the eukaryotic DNA replication fork. J. Biol. Chem. 284, 4041-4045. [PubMed]
Yao, N.Y., and O'Donnell, M. (2010). SnapShot: The replisome. Cell 141, 1088. [PubMed]

Separating parental strands
Figure: 3-9, 3-10.
Reference:
West, S.C. (1996). DNA helicases: new breeds of translocating motors and molecular pumps. Cell 86, 177-180.
Additional reference:
Berger, J.M. (2008). SnapShot: nucleic acid helicases and translocases. Cell 134, 888-888. [PubMed]
Takara, T.J., and Bell, S.P. (2009). Putting two heads together to unwind DNA. Cell 139, 652-654. [PubMed]

Box 3-2. Topoisomerases and anti-cancer drugs
Reference:
Wang, J.C. (1991). DNA topoisomerases: why so many? J. Biol. Chem. 266, 6659-6662.
Berger, J.M., Gamblin, S.J., Harrison, S.C. and Wang, J.C. (1996). Structure and mechanism of DNA topoisomerase II. Nature 379, 225-232. [PubMed]
Additional reference:
Nitiss, J.L. (2009). Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer 9, 338-350. [PubMed]
Pommier, Y., Sun, Y., Huang, S.N., Nitiss, J.L. (2016). Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat. Rev. Mol. Cell Biol. 17, 703-721. [PubMed]

RNA primers
Additional reference:
Lao-Sirieix, S.H., Pellegrini, L., and Bell, S.D. (2005). The promiscuous primase. Trends Genet. 21, 568-572. [PubMed]

The asymmetric fork
Figure: 3-11, 3-12, 3-13, 3-14, 3-15.
Reference:
Ogawa, T. and Okazaki, T. (1980). Discontinuous DNA replication. Annu. Rev. Biochem. 49, 421-457.
Stukenberg, P.T., Studwell-Vaughan, P.S. and O'Donnell, M. (1991). Mechanism of the sliding beta-clamp of DNA polymerase III holoenzyme. J. Biol. Chem. 266, 11328-11334. [PubMed]
Krishna, T.S., Kong, X.P., Gary, S., Burgers, P.M. and Kuriyan, J. (1994). Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell 79, 1233-1243. [PubMed]
Wyman, C. and Botchan, M. (1995). A familiar ring to DNA polymerase processivity. Current Biol. 5, 334-337. [PubMed]
Hozák, P., Jackson, D.A. and Cook. P.R. (1996). The role of nuclear structure in DNA replication. In 'Eukaryotic DNA replication: frontiers in molecular biology' (Ed. J.J. Blow), pp124-142. Oxford University Press, Oxford.
Waga, S. and Stillman, B. (1998). The DNA replication fork in eukaryotic cells. Annu Rev. Biochem. 67, 721-751. [PubMed]
Additional reference:
Burgers, P.M. (2009). Polymerase dynamics at the eukaryotic DNA replication fork. J. Biol. Chem. 284, 4041-4045. [PubMed]
Moldovan, G.L., Pfander, B., and Jentsch, S. (2007). PCNA, the maestro of the replication fork. Cell 129, 665-679. [PubMed]
Shuman, S. (2009). DNA ligases: progress and prospects. J. Biol. Chem. 284, 17365-17369. [PubMed]
Yao, N.Y., and O'Donnell, M. (2009). Replisome structure and conformational dynamics underlie fork progression past obstacles. Curr. Opin. Cell Biol. 21, 336-343. [PubMed]

Proofreading
Figure: 3-16.
Reference:
Echols, H. and Goodman, M.F. (1991). Fidelity mechanisms in DNA replication. Annu Rev. Biochem. 60, 477-511.
Additional reference:
Francklyn, C.S. (2008). DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression. Biochemistry 47, 11695-11703. [PubMed]
McCulloch, S.D., and Kunkel, T.A. (2008). The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell 18, 148-161. [PubMed]
Storchova, Z., and Kuffer, C. (2008). The consequences of tetraploidy and aneuploidy. J. Cell Sci. 121, 3859-3866. [PubMed]

Replicating chromatin
Reference:
Krude, T. (1999). Chromatin assembly during DNA replication in somatic cells. Eur. J. Biochem. 263, 1-5. [PubMed] [Full text]
Additional reference:
Probst, A.V., Dunleavy, E., and Almouzni, G. (2009). Epigenetic inheritance during the cell cycle. Nat. Rev. Mol. Cell Biol 10, 192-206. [PubMed]
Smith, D.J., and Whitehouse, I. (2012). Intrinsic coupling of lagging-strand synthesis to chromatin assembly. Nature 483, 434-438. [PubMed]

The initiation of synthesis
Figure: 3-17.
Reference:
Huberman, J.A. and Riggs, A.D. (1968). On the mechanism of DNA replication in mammalian chromosomes. J. Mol. Biol. 75, 327-341.
DePamphilis, M.L. (1999). Replication origins in metazoan chromosomes: fact or fiction? BioEssays 21, 5-16. [PubMed]
Additional reference:
Hamlin, J.L., Mesner, L.D., and Dijkwel, P.A. (2010). A winding road to origin discovery. Chromosome Res. 18, 45-61. [PubMed]
Robinson, N.P. and Bell, S.D. (2005).  Origins of DNA replication in the three domains of life.  FEBS J. 272, 3757-3766. [PubMed]

Box 3-3. The origin of replication of E. coli
Reference:
Sugimoto, K., Oka, A., Sugisaki, H., Takanam, M., Nishimura, A., Yasuda, Y. and Hirota, Y. (1979). Nucleotide sequence of Escherichia coli K-12 replication origin. Proc. Natl. Acad. Sci. USA 76, 575-579. [PubMed]
Additional reference:
Duderstadt, K.E., and Berger, J.M. (2008). AAA+ ATPases in the initiation of DNA replication. Crit. Rev. Biochem. Mol. Biol. 43, 163-187. [PubMed]
Ozaki, S., and Katayama, T. (2009). DnaA structure, function, and dynamics in the initiation at the chromosomal origin. Plasmid 62, 71-82. [PubMed]

Simple origins of SV40 virus and yeast
Reference:
Borowiec, J.A., Dean, F.B., Bullock, P.A. and Hurwitz, J. (1990). Binding and unwinding - how T antigen engages the SV40 origin of DNA replication. Cell 60, 181-184.
Bell, S.P. and Stillman, B. (1992). ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357, 128-134. [PubMed]
Marahrens, Y. and Stillman, B. (1996). The initiation of DNA replication in the yeast Saccharomyces cerevisiae. In 'Eukaryotic DNA replication' (Ed. Blow, J.J.), pp 66-95. Oxford University Press, Oxford.
Additional reference:
Duderstadt, K.E., and Berger, J.M. (2008). AAA+ ATPases in the initiation of DNA replication. Crit. Rev. Biochem. Mol. Biol. 43, 163-187. [PubMed]
Hamlin, J.L., Mesner, L.D., and Dijkwel, P.A. (2010). A winding road to origin discovery. Chromosome 18, 45-61. [PubMed]
Fanning, E., and Zhao, K. (2009). SV40 DNA replication: from the A gene to a nanomachine. Virology 384, 352-359. [PubMed]
Raghuraman, M.K., and Brewer, B.J. (2010). Molecular analysis of the replication program in unicellular model organisms. Chromosome 18, 19-34. [PubMed]
Robinson, N.P. and Bell, S.D. (2005).  Origins of DNA replication in the three domains of life.  FEBS J. 272, 3757-3766. [PubMed]

Box 3-4. Methods for mapping origins
Figure: 3-18A, 3-18B.
Reference:
Brewer, B.J. and Fangman, W.L. (1987). The localization of replication origins on ARS plasmids in S. cerevisiae. Cell 51, 463-471. [PubMed]
Vassilev, L. and Johnson, E.M. (1989). Mapping initiation sites of DNA replication in vivo using polymerase chain amplification of nascent strand segments. Nucleic Acids Res. 17, 7693-7705. [PubMed]
Additional reference:
Cadoret, J.C., and Prioleau, M.N. (2010). Genome-wide approaches to determining origin distribution. Chromosome Res. 18, 79-89. [PubMed]
Bielinsky, A.-K. and Gerbi, S.A. (2001). Where it all starts: eukaryotic origins of DNA replication. J. Cell Sci. 114, 643-651. [PubMed]
Friedman, K.L. and Brewer, B.J. (1995). Analysis of replication intermediates by two-dimensional agarose gel electrophoresis. Methods Enzymol. 130, 613-627.

Complex mammalian origins
Reference:
Harland, R.M. and Laskey, R.A. (1980). Regulated replication of DNA microinjected into eggs of Xenopus laevis. Cell 21, 761-771. [PubMed]
Craig, J.M. and Bickmore, W.A. (1993). Chromosome bands - flavours to savour. BioEssays 15, 349-354. [PubMed]
Jackson, D.A. and Pombo, A. (1998). Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to efficient activation and propogation of S phase in human cells. J. Cell Biol. 140, 1285-1295. [PubMed] [Full text]
Dimitrova, D.S. and Gilbert, D.M. (1999). The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Mol. Cell 4, 983-993. [PubMed]
Additional reference:
Creager, R.L., Li, Y., and MacAlpine, D.M. (2015). SnapShot: Origins of DNA Replication. Cell 161, 418-418. [PubMed]
Fragkos, M., Ganier, O., Coulombe, P., and Méchali, M. (2015). DNA replication origin activation in space and time. Nat. Rev. Mol. Cell Biol. 16, 360-374. [PubMed]
Mesner, L.D., Crawford, E.L., and Hamlin, J.L. (2006).  Isolating apparently pure libraries of replication origins from complex genomes.  Mol. Cell 21, 719-726. [PubMed]
Pope, B.D., Ryba, T., Dileep, V., Yue, F., Wu, W., Denas, O., Vera, D.L., Wang, Y., Hansen, R.S., Canfield, T.K., Thurman, R.E., Cheng. Y., Gülsoy, G., Dennis, J.H., Snyder, M.P., Stamatoyannopoulos, J.A., Taylor, J., Hardison, R.C., Kahveci, T., Ren, B., and Gilbert, D.M. (2014). Topologically associating domains are stable units of replication-timing regulation. Nature 515, 402-405. [PubMed]
Yeeles, J.T., Deegan, T.D., Janska, A., Early, A., and Diffley, J.F. (2015). Regulated eukaryotic DNA replication origin firing with purified proteins. Nature 519, 431-435. [PubMed]

Role of transcription during initiation
Figure: 3-19, 3-20.
Reference:
Hassan, A.B., Errington, R.J., White, N.S., Jackson, D.A. and Cook. P.R. (1994). Replication and transcription sites are colocalized in human cells. J. Cell Sci. 107, 425-434. [PubMed] [Full text]
Additional reference:
Danis, E., Brodolin, K., Menut, S., Maiorano, D., Girard-Reydet, C. and Mechali, M. (2004).  Specification of a DNA replication origin by a transcription complex.  Nat. Cell Biol. 6, 721-730.  [PubMed]
Dellino, G.I., Cittaro, D., Piccioni, R., Luzi, L., Banfi, S., Segalla, S., Cesaroni, M., Mendoza-Maldonado, R., Giacca, M., and Pelicci, P.G. (2013). Genome-wide mapping of human DNA-replication origins: levels of transcription at ORC1 sites regulate origin selection and replication timing. Genome Res. 23, 1-11. [PubMed]

Replicating ends
Figure: 3-21, 3-22.
Reference:
Hozák, P., Jackson, D.A. and Cook. P.R. (1996). The role of nuclear structure in DNA replication. In 'Eukaryotic DNA replication: frontiers in molecular biology' (Ed. J.J. Blow), pp124-142. Oxford University Press, Oxford.
Nugent, C.I. and Lundblad, V. (1998). The telomerase reverse transcriptase: components and regulation. Genes Dev. 12, 1073-1085. [Full text]
Additional reference:
Blackburn, E.H. (2005). Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett. 579, 859-862. [PubMed]
Mason, M., Schuller, A., and Skordalakes, E. (2011). Telomerase structure function. Curr. Opin. Struct. Biol. 21, 92-100. [PubMed]

Box 3-5. Telomerase in ageing and cancer
Reference:
Zakian, V.A. (1997). Life and cancer without telomerase. Cell 91, 1-3.
Greider, C.W. (1998). Telomerase activity, cell proliferation, and cancer. Proc. Natl. Acad. Sci. USA 95, 90-92. [Full text]
Additional reference:
Lansdorp, P.M. (2009). Telomeres and disease. EMBO J. 28, 2532-2540. [PubMed]

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