Nuclear Structure and Function Research Group

Resources for CHAPTER 1: SOME PRINCIPLES
Updated on 17 October, 2016

Overview of the cell nucleus
        Box 1-1. Discovery of cells, nuclei, and DNA
A sense of scale
        Box 1-2. Microscopy: problems and solutions
        Box 1-3. Green fluorescent protein
    Thermal motion
    Local concentrations
Structures of nucleic acids
    The DNA double helix
        Box 1-4. Translation
    The length of DNA molecules
        Box 1-5. Gel electrophoresis and blotting
    Bending and twisting DNA
    The structure of RNA
Recognizing specific DNA sequence
        Box 1-6. DNA:protein binding - 'gel-shifts', 'footprinting', 'ChIP'
    DNA-binding proteins
        Box. Genome editing
Making large structures
    Assembling nuclei in egg extracts
    Subcellular localization
    Generating asymmetric structures
    Tensegrity architecture and cellular skeletons
    Nuclear position and shape
Some evolutionary considerations
    Genome size
        Box 1-7. The amount of DNA in a human nucleus
    Regulatory networks: redundant, robust, and noisy
        Box 1-8. Protein:protein interactions - 'two-hybrid', 'FRET'
        Box 1-9. Simulating complex control circuits
    Sub-compartments and the origin of nuclei
        Box 1-10. The three primary lineages of the living world

Overview of the cell nucleus
Figure: 1-1.
Web link:
http://www.accessexcellence.org/AB/GG/ National Health Museum page of various molecules and cellular structures.
http://micro.magnet.fsu.edu/cells/nucleus/nucleus.html From Molecular Expressions.

Box 1-1. Discovery of cells, nuclei, and DNA
Reference:
Gall, J.G. (1996). 'A pictorial history: views of the cell'. American Society of Cell Biology, Bethesda, Maryland.
Harris, H. (1999). 'The birth of the cell'. Yale University Press, New Haven and London.
Additional reference:
Zacharias, H. (2001). Key word: chromosome. Chromosome Research 9, 345-355. [PubMed]
Web link:
http://www.mendelweb.org/  Classical genetics.

A sense of scale
Table: 1-1.
Figure: 1-2.
Reference:
Goodsell, D.S. (1993). 'The machinery of life'. Springer-Verlag, New York.
Additional reference:
Frenkiel-Krispin, D., Ben-Avraham, I., Englander, J., Shimoni, E., Wolf, S.G. and Minsky, A. (2004).  Nucleoid restructuring in stationary-state bacteria.  Mol. Microbiol. 51, 395-405.  [PubMed]
Minton, A.P. (2006). Macromolecular crowding. Curr. Biol. 16, R269-R271. [PubMed]
Moran, U., Phillips, R., and Milo, R. (2010). SnapShot: key numbers in biology. Cell 141, 1262-1262. [PubMed]
Web link:
http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/poster_full.pdf Proteins to scale.
http://www.scripps.edu/pub/goodsell/ Cells and their contents drawn to scale.
http://www.nbr.wisc.edu/imr.html Dig into the National Biophotonics Resource, USA, for images.
http://learn.genetics.utah.edu/content/begin/cells/scale/ Primer from the University of Utah.

Box 1-2. Microscopy: problems and solutions
Reference:
Bozzola, J.J. and Russell, L.D. (1992). 'Electron microscopy: principles and techniques for biologists'. Jones and Bartlett, Boston.
Oldfield, R. (1994). 'Light microscopy: an illustrated guide'. Wolfe, London.
Additional reference:
Cheng Y. (2015). Single-particle cryo-EM at crystallographic resolution. Cell 161, 450-457. [PubMed]
Galbraith CG., and Galbraith JA. (2011). Super-resolution microscopy at a glance. J Cell Sci. 124, 1607-1611. [PubMed]
Heuser, J. (2002).  Whatever happened to the 'microtrabecular concept'?  Biol. Cell. 94, 561-596.  [PubMed]
Johnson, J. (2012). Not seeing is not believing: improving the visibility of your fluorescence images. Mol. Biol. Cell 23, 754-757. [PubMed]
Kasper, R., and Huang, B. (2011). SnapShot: light microscopy. Cell 147, 1198-1198. [PubMed]
Liu, Z., Lavis, L.D., and Betzig, E. (2015). Imaging live-cell dynamics and structure at the single-molecule level. Mol. Cell 58, 644-659. [PubMed]
Lucic, V., Rigort, A., and Baumeister, W. (2013). Cryo-electron tomography: The challenge of doing structural biology in situ. J. Cell Biol 202, 407-419. [PubMed]
Roeder, A,H., Cunha, A., Burl, M.C., and Meyerowitz, E.M. (2012). A computational image analysis glossary for biologists. Development 139, 3071-3080. [PubMed]
Ronneberger, O., Baddeley, D., Scheipl, F., Verveer, P.J., Burkhardt, H., Cremer, C., Fahrmeir, L., Cremer, T., and Joffe, B. (2008). Spatial quantitative analysis of fluorescently labeled nuclear structures: Problems, methods, pitfalls. Chromosome Res. 16, 523-562. [PubMed]
Saper, C.B. (2009). A quide to the perplexed on the specificity of antibodies. J. Histochem. Cytochem. 57, 1-5. [PubMed]
Wineya, M., Meehla, J.B., O'Toole, E.T., and Giddings, T.H Jr. (2014). Conventional transmission electron microscopy. Mol. Biol. Cell 25, 319-923. [PubMed]
Web link:
http://www.nasa.gov/offices/education/centers/kennedy/technology/Virtual_Lab.html Download and use a virtual scanning EM from NASA's 'Classroom' and 'Virtual lab'.
http://www.microscopy.fsu.edu/primer/ Good tutorials on 3-D microscopy from Molecular Expressions.
http://micro.magnet.fsu.edu/index.html Microscopy page from Molecular Expressions.
http://micro.magnet.fsu.edu/primer/virtual/confocal/index.html Confocal microscopy from Molecular Expressions.
http://www.microscopyu.com Nikon's site with tutorials on various aspects of microscopy.
http://www.olympusmicro.com/index.html Olympus' site with various interactive tutorials.
http://www.olympusmicro.com/primer/virtual/virtual.html Olympus' virtual microscopes.

Box 1-3. Green fluorescent protein
Figure: 1-2.
Reference:
Tsien, R.Y. (1998). The green fluorescent protein. Annu. Rev. Biochem. 67, 509-544. [PubMed]
Additional reference:
Chalfie, M. (2009). GFP: lighting up life. Proc. Natl. Acad. Sci. USA 106, 10073-10080. [PubMed]
Frigault, M.M., Lacoste, J., Swift, J.L., and Brown, C.M. (2009). Live-cell microscopy - tips and tools. J. Cell Sci. 122, 753-767. [PubMed]
Giepmans, B.N., Adams, S.R., Ellisman, M.H., and Tsien, R.Y. (2006). The fluorescent toolbox for assessing protein location and function. Science 312, 217-224. [PubMed]
Janicki, S.M., Tsukamoto, T., Salghetti, S.E., Tansey, W.P., Sachidanandam, R., Prasanth, K.V., Ried, T., Shav-Tal, Y., Bertrand, E., Singer, R.H. and Spector, D.L. (2004).  From silencing to gene expression; real-time analysis in single cells.  Cell 116, 683-698.  [PubMed]
Mueller, F., Mazza, D., Stasevich, T.J., and McNally, J.G. (2010). FRAP and kinetic modeling in the analysis of nuclear protein dynamics: what do we really know? Curr. Opin. Cell Biol. 22, 403-411. [PubMed]
Web link:
http://www.clontech.com/products/detail.asp?product_family_id=1417&product_group_id=209303&product_id=10419 Page of a supplier.
http://jcs.biologists.org/cgi/reprint/114/5/837.pdf  Fluorescent protein spectra.

Thermal motion
Reference:
Goodsell, D.S. (1993). 'The machinery of life'. Springer-Verlag, New York.
Marshall, W.F., Straight, A., Marko, J.F., Swedlow, J., Dernburg, A., Belmont, A., Murray, A.W., Agard, D.A. and Sedat, J.W. (1997). Interphase chromosomes undergo constrained diffusional motion in living cells. Curr. Biol. 7, 930-939. [PubMed]
Additional reference:
Lippincott-Schwartz, J., Altan-Bonnet, N,. and Patterson, G.H. (2003). Photobleaching and photoactivation: following protein dynamics in living cells. Nat. Cell Biol. Suppl: S7-14. [PubMed]
Misteli, T. (2001). Protein dynamics: implications for nuclear architecture and gene expression. Science 291, 843-847. [PubMed]
Web link:
http://www.uic.edu/classes/phys/phys461/phys450/ Biophysics of cells and molecules from Anjum Ansari and John F. Marko (University of Illinois at Chicago).

Local concentrations 
Additional reference:
Guantes, R., Rastrojo, A., Neves, R., Lima, A., Aguado, B., and Iborra, F.J. (2015). Global variability in gene expression and alternative splicing is modulated by mitochondrial content. Genome Res. 25, 633-644. [PubMed]
Minton, A.P. (2006). Macromolecular crowding. Curr. Biol. 16, R269-R271. [PubMed]
Marenduzzo, D., Finan, K., and Cook, P.R. (2006). The depletion attraction: an underappreciated force driving cellular organization. J. Cell Biol. 175, 681-686. [PubMed]
Zhou, Z.H., McCarthy, D.B., O'Connor, C.M., Reed, L.J. and Stoops, J.K. (2001). The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Proc. Natl. Acad. Sci. USA 98, 14802-14807. [PubMed] [Full text]
Web link:
http://www.scripps.edu/pub/goodsell/ Cells and their contents drawn to scale.

Structures of nucleic acids
Figure: 1-3, 1-4.
Reference:
Blackburn, G.M. and Gait, M.J. (1990). 'Nucleic acids in chemistry and biology'. IRL Press, Oxford.
Web link:
http://www.accessexcellence.org/AB/GG/ National Health Museum page of various molecules and cellular structures. 
http://www.imb-jena.de/IMAGE.html Library of Biological Macromolecules.
http://www.umass.edu/microbio/rasmol/ This site tells where to get - and how to use - free software to visualize 3D molecular structures, including DNA.

The DNA double helix
Figure: 1-5, 1-6, 1-7.
Reference:
Watson, J.D. and Crick. F.H.C. (1953a). Molecular structure of nucleic acids: a structure of deoxyribonucleic acid. Nature 171, 737-738. [Web link]
Watson, J.D. and Crick. F.H.C. (1953b). Genetic implications of the structure of deoxyribonucleic acid. Nature 171, 964-967. [Web link]
Additional reference:
Agris, P.F. (2004).  Decoding the genome: a modified view.  Nucleic Acids Res. 32, 223-238.  [PubMed]
Chin, J.W. (2012). Reprogramming the genetic code. Science 336, 428-429. [PubMed]
Kresge, N., Simoni, R.D. and Hill, R.L. (2005).  Using tryptophan synthase to prove gene-protein colinearity: the work of Charles Yanofsky. J. Biol. Chem. 280, e43. [PubMed]
Nirenberg, M. (2004). Deciphering the genetic code - a personal account.  Trends Biochem. Sci. 29, 46-54.  [PubMed]
Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang, S., Chaput, J.C., Wengel, J., Peak-Chew, S.Y., McLaughlin, S.H., Herdewijn, P., and Holliger, P. (2012). Synthetic genetic polymers capable of heredity and evolution. Science 336, 341-344. [PubMed]
Rich, A. (2006).  Discovery of the hybrid helix & the first DNA-RNA hybridization.  J. Biol. Chem. 281, 7693-7696.  [PubMed]
Sarafianos, S.G., Arnold, E. (2008). RT slides home... Science 322, 1059-1060. [PubMed]
Wells, R.D. (2007). Non-B DNA conformations, mutagenesis and disease. Trends Biochem. Sci. 32, 271-278. [PubMed]
Yanofsky, C. (2007). Establishing the triplet nature of the genetic code. Cell 128, 815-818. [PubMed]
Web link:
http://www.nature.com/nature/dna50/archive.html Nature's page with the original articles by Watson and Crick.
http://www.nature.com/nature/dna50/Crick3.pdf Francis Crick looks back on the discovery of DNA.
http://www.accessexcellence.org/AB/GG/ National Health Museum page gives images of DNA and its components.
http://learn.genetics.utah.edu/content/begin/dna/builddna/ Primer from the University of Utah.
http://learn.genetics.utah.edu/content/begin/tour/ Genetics primer from the University of Utah

Box 1-4. Translation
Table: 1-2.
Reference:
Cech, T.R. (2000). The ribosome is a ribozyme. Science 289, 878-879.  [PubMed]
Additional reference:
This box has been expanded into a new chapter.

The length of DNA molecules
Figure: 1-8.
Reference:
Schwartz, D.C. and Cantor, C.R. (1984). Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell 37, 67-75. [PubMed]
Carle, G.F. and Olson, M.V. (1984). Separation of chromosomal DNA molecules from yeast by orthogonal-field-alternation gel electrophoresis. Nucl. Acids Res. 12, 5647-5664. [PubMed]
Griffith, J.D., Comeau, L., Rosenfeld, S., Stansel, R.M., Bianchi, A., Moss, H. and de Lange, T. (1999). Mammalian telomeres end in a large duplex loop. Cell 97, 503-514. [PubMed]
Additional reference:
Bendich, A.J. (2001). The form of chromosomal DNA molecules in bacterial cells. Biochimie 83, 177-186. [PubMed]
Wrestler, J.C., Lipes, B.D., Birren, B.W. and Lai, E. (1996). Pulsed-field gel electrophoresis. Methods Enzymol. 272, 255-272.
Web link:
http://biotech.matcmadison.edu/resources/activities/dna/default.htm How to make DNA from a smoothie in a few minutes - an experiment everyone should do once in a lifetime.

Box 1-5. Gel electrophoresis and blotting
Reference:
Schwartz, D.C. and Cantor, C.R. (1984). Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell 37, 67-75. [PubMed]
Carle, G.F. and Olson, M.V. (1984). Separation of chromosomal DNA molecules from yeast by orthogonal-field-alternation gel electrophoresis. Nucl. Acids Res. 12, 5647-5664. [PubMed]
Hames, B.D. (1998). 'Gel electrophoresis of proteins: a practical approach'. 3^rd Ed. Oxford University Press, Oxford.
Additional reference:
Pederson, T. (2008). Turning a PAGE: the overnight sensation of SDS-polyacrylamide gel electrophoresis. FASEB J. 22, 949-953. [PubMed]
Web link:
http://learn.genetics.utah.edu/content/labs/gel/ Primer from the University of Utah.

Bending and twisting DNA
Figure: 1-9.
Reference:
Wasserman, S.A. and Cozzarelli, N.R. (1986). Biochemical topology: application to DNA recombination and replication. Science 232, 951-960. [PubMed]
Calladine, C.R. and Drew, H.R. (1992). 'Understanding DNA: the molecule and how it works'. Academic Press, London.
Additional reference:
Bryant, Z., Stone, M.D., Gore, J., Smith, S.B., Cozzarelli, N.R. and Bustamante, C. (2003).  Structural transitions and elasticity from torque measurements on DNA.  Nature 424, 338-341.  [PubMed]
Cozzarelli, N.R., Cost, G.J., Nollmann, M., Viard, T., and Stray, J.E. (2006). Giant proteins that move DNA: bullies of the genomic playground. Nat. Rev. Mol. Cell Biol. 7, 580-588. [PubMed]
Ohyama, T. (2001). Intrinsic DNA bends: an organizer of local chromatin structure for transcription. Bioessays 23, 708-715. [PubMed]
Web link:
http://www.msri.org/publications/ln/msri/2000/molbio/sumners/1/ DNA knots.
http://alice.berkeley.edu/content/movies.php Movies of DNA from C. Bustamente.

The structure of RNA
Figure: 1-10, 1-11.
Reference:
Blackburn, G.M. and Gait, M.J. (1990). 'Nucleic acids in chemistry and biology'. IRL Press, Oxford.
Additional reference:
Agris, P.F. (2004).  Decoding the genome: a modified view.  Nucleic Acids Res. 32, 223-238.  [PubMed]
Kresge, N., Simoni, R.D., and Hill, R.L. (2005).  The Discovery of tRNA by Paul C. Zamecnik.  J. Biol. Chem. 280, e37.  [PubMed]
Web link:
http://www.accessexcellence.org/AB/GG/ National Health Museum page of various molecules and cellular structures.

Recognizing specific DNA sequences
Figure: 1-12, 1-13.
Reference:
Werner, M.H. and Burley, S.K. (1997). Architectural transcription factors: proteins that remodel DNA. Cell 88, 733-736.  [PubMed]

Box 1-6. DNA:protein binding - 'gel-shifts', 'footprinting', 'ChIP'
Reference:
Sauer, R.T. (1991). Protein-DNA interactions. Meth. Enzymol. 208, 1-700.
Kneale, G.G. (1994). 'DNA-protein interactions: principles and protocols'. Chapman and Hall, New York.
Cosma, M.P., Tanaka, T. and Nasmyth, K. (1999). Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally-regulated promoter. Cell 97, 299-311. [PubMed]
Additional reference:
Iyer, V.R., Horak, C.E., Scarfe, C.S., Botstein, D., Snyder, M. and Brown, P.O. (2001). Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409, 533-538. [PubMed]
Mackay, J.P., Sunde, M., Lowry, J.A., Crossley, M., and Matthews, J.M. (2007). Protein interactions: is seeing believing? Trends Biochem. Sci. 32, 530-531. [PubMed]
Pollard, T.D. (2010). A guide to simple and informative binding assays. Mol. Biol. Cell 21, 4061–4067. [PubMed]

DNA-binding proteins
Figure: 1-14.
Reference:
Patikoglou, G. and Burley, S.K. (1997). Eukaryotic transcription factor-DNA complexes. Annu. Rev. Biophys. Biomol. Struct. 26, 289-325. [PubMed]
Additional reference:
Baldwin, R.L. (2002). Protein folding: making a network of hydrophopic clusters. Science 295, 1657-1658. [PubMed]
Cozzarelli, N.R., Cost, G.J., Nollmann, M., Viard, T., and Stray, J.E. (2006). Giant proteins that move DNA: bullies of the genomic playground. Nat. Rev. Mol. Cell Biol. 7, 580-588. [PubMed]
Howarth M. (2015). Say it with proteins: an alphabet of crystal structures. Nat. Struct. Mol. Biol. 22, 349. [PubMed]
Kuhlman, B. and Baker, D. (2000).  Native protein sequences are close to optimal for their structures.  Proc. Natl. Acad. Sci. USA 97, 10383-10388.  [PubMed]
Web link:
http://www.expasy.ch The Swiss Institute of Bioinformatics (SIB) contains many protein structures.
http://scop.mrc-lmb.cam.ac.uk/scop/ Database of modules used to build proteins.
http://www.pnas.org/misc/classics1.shtml Some original papers on protein structures by Pauling and Corey.

Box. Genome editing
Additional reference:
Doudna, J.A., and Charpentier, E. (2014). Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096. [PubMed]
Konermann, S., Brigham, M.D., Trevino, A.E., Joung, J., Abudayyeh, O.O., Barcena, C., Hsu, P.D., Habib, N., Gootenberg, J.S., Nishimasu, H., Nureki, O., and Zhang, F. (2015). Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517, 583-588. [PubMed]
McMahon, M.A., Rahdar, M., and Porteus, M. (2012). Gene editing: not just for translation anymore. Nat. Methods 9, 28-31. [PubMed]
de Souza, N. (2012). Primer: genome editing with engineered nucleases. Nat. Methods 9, 27. [PubMed]

Making large structures
Figure: 1-15.
Reference:
Caspar, D.L.D. and Klug, A. (1962). Physical principles in the construction of regular viruses. Cold Spring Harbor Symp. Quant. Biol. 27, 1-24.
Additional reference:
Alber, F., Dokudovskaya, S., Veenhoff, L.M., Zhang, W., Kipper, J., Devos, D., Suprapto, A., Karni-Schmidt, O., Williams, R., Chait, B.T., Rout, M.P., and Sali, A. (2007). Determining the architectures of macromolecular assemblies. Nature 450, 683-694. [PubMed]
Fersht, A.R.and Daggett, V. (2002). Protein folding and unfolding at atomic resolution. Cell 108, 573-582. [PubMed]
Karsenti, E. (2008). Self-organization in cell biology: a brief history. Nat. Rev. Mol. Cell Biol. 9, 255-262. [PubMed]
Misteli, T. (2005). Concepts in nuclear architecture. Bioessays 27, 477-487. [PubMed]
Rafelski, S.M., and Marshall, W.F. (2008). Building the cell: design principles of cellular architecture. Nat. Rev. Mol. Cell Biol. 9, 593-602. [PubMed]
Service RF. (2008). Problem solved* (*sort of). Science 321, 784-786. [PubMed]

Assembling nuclei in egg extracts
Reference:
Wolffe, A. (1998). 'Chromatin: structure and function'. 3^rd edition. Academic Press, London.
Additional reference:
Brown, D.D. (2004). A tribute to the Xenopus laevis oocyte and egg. J. Biol. Chem. 279, 45291-45299. [PubMed]

Subcellular localization
Reference:
Andrade, M.A., O'Donoghue, S.I. and Rost, B. (1998). Adaptation of protein surfaces to subcellular location. J. Mol. Biol. 276, 517-525. [PubMed] [Full text]
Additional reference:
Donnes, P., and Hoglund, A. (2004). Predicting protein subcellular localization: past, present, and future. Genomics Proteomics Bioinformatics 2, 209-215. [PubMed]

Tensegrity architecture and cellular skeletons
Reference:
Forgacs, G. (1995). On the possible role of cytoskeletal filamentous networks in intracellular signalling: an approach based on percolation. J. Cell Sci. 108, 2131-2143. [Full text]
Chicurel, M.E., Chen, C.S. and Ingber, D.E. (1998). Cellular control lies in the balance of forces. Curr. Opin. Cell Biol. 10, 232-239. [PubMed]
Gundersen, G.G. and Cook, T.A. (1999). Microtubules and signal transduction. Curr. Opin. Cell Biol. 11, 81-94. [PubMed] 
Additional reference:
Callaway, E. (2008). Bacteria's new bones. Nature 451, 124-126. [PubMed]
Wickstead, B., and Gull, K. (2011). The evolution of the cytoskeleton. J. Cell Biol. 194, 513-525. [PubMed]
Ingber, D.E. (2006). Cellular mechanotransduction: putting all the pieces together again. FASEB J. 20, 811-827. [PubMed]
Pollard, T.D., and Cooper, J.A. (2009). Actin, a central player in cell shape and movement. Science 326, 1208-1212. [PubMed]
Rohn, J.L., and Baum, B. (2010). Actin and cellular architecture at a glance. J. Cell Sci. 123, 155-158. [PubMed]
Web link:
Try searching for 'tensegrity' and you will find lots of pages.

Generating asymmetrical structures
Additional reference:
Green, J.B., and Sharpe, J. (2015). Positional information and reaction-diffusion: two big ideas in developmental biology combine. Development 142, 1203-1211. [PubMed]
Macara, I.G., and Mili, S. (2008). Polarity and differential inheritance – universal attributes of life? Cell 135, 801-812. [PubMed]
Marshall, W.F. (2011). Origins of cellular geometry. BMC Biol. 9, 57. [PubMed]

Nuclear position and shape
Reference:
Thompson, D.W. (1959). 'On growth and form'. 2nd Edition. Cambridge University Press, Cambridge.
Reinsch, S. and Gönczy, P. (1998). Mechanisms of nuclear positioning. J. Cell Sci. 111, 2283-2295. [PubMed] [Full text]
Additional reference:
Burke, B., and Roux, K.J. (2009). Nuclei take a position: managing nuclear location. Dev. Cell 17, 587-597. [PubMed]
Daga, R.R., Yonetani, A., and Chang, F. (2006). Asymmetric microtubule pushing forces in nuclear centering. Curr. Biol. 16, 1544-1550. [PubMed]
Huber, M.D., and Gerace, L. (2007). The size-wise nucleus: nuclear volume control in eukaryotes. J. Cell Biol. 179, 583-584. [PubMed]
Marshall, W.F. (2011). Origins of cellular geometry. BMC Biol. 9, 57. [PubMed]
Metzger, T., Gache, V., Xu, M., Cadot, B., Folker, E.S., Richardson, B.E., Gomes, E.R., and Baylies, M.K. (2012). MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature 484, 120-124. [PubMed]
Mijaljica, D., and Devenish, R.J. (2013). Nucleophagy at a glance. J. Cell Sci. 126, 4325-4330. [PubMed]
Moseley, J.B., and Nurse, P. (2010). Cell division intersects with cell geometry. Cell 142, 184-188. [PubMed]
Solovei, I., Kreysing, M., Lanctôt, C., Kösem, S., Peichl, L., Cremer, T., Guck, J., and Joffe, B. (2009). Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137, 356–368. [PubMed]
Webster, M., Witkin, K.L., and Cohen-Fix, O. (2009). Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly. J Cell Sci 122, 1477-1486. [PubMed]

Some evolutionary considerations
Reference:
Howard, J. (1982). 'Darwin'. Oxford University Press, Oxford.
Additional reference:
Bowler, P.J. (2009). Darwin's originality. Science 323, 223-226. [PubMed]
Jones, D. (1999). 'Almost like a whale: the origin of species updated'. Doubleday. London and New York.
Szostak, J.W. (2009). Origins of life: systems chemistry on early earth. Nature 459, 171-172. [PubMed]
Lynch, M., and Marinov, G.K. (2015). The bioenergetic costs of a gene. Proc Natl Acad Sci USA 112, 15690-15695. [PubMed]
Webber, C., and Ponting, C.P. (2004). Genes and homology. Curr Biol. 14, R332-333. [PubMed]
Web link:
http://darwin-online.org.uk/ The writings of Charles Darwin.
http://www.ucmp.berkeley.edu/history/evolution.html Museum of Paleontology at the University of California, Berkeley.

Genome size
Figure: 1-16.
Reference:
Jelinek, W.R. and Schmid, C.W. (1982). Repetitive sequences in eukaryotic DNA and their expression. Annu Rev. Biochem. 51, 813-844.  [PubMed]
Kazazian, H,H, (2000). L1 retrotransposons shape the mammalian genome. Science 289, 1152-1153. [PubMed]
Additional reference:
Belancio, V.P., Hedges, D.J., and Deininger, P. (2008). Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res. 18, 343-358. [PubMed]
Cordaux, R. (2008). The human genome in the LINE of fire. Proc. Natl. Acad. Sci. USA 105, 19033-19034. [PubMed]Doolittle, W.F. (2013). Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. USA 110, 5294-5300. [PubMed]
Eddy SR. (2012). The C-value paradox, junk DNA and ENCODE. Curr. Biol. 22, R898-899. [PubMed]
Mariner, P.D., Walters, R.D., Espinoza, C.A., Drullinger, L.F., Wagner, S.D., Kugel, J.F., Goodrich, J.A. (2008). Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol. Cell 29, 499-509. [PubMed]
Lane, N., and Martin, W. (2010). The energetics of genome complexity. Nature 467, 929-934. [PubMed]
Web link:
http://www.nature.com/genomics/Nature's Genome Gateway.
http://nar.oupjournals.org/ Go to the Database issue of Nucleic Acids Research, which describes many different on-line databases.

Box 1-7. The amount of DNA in a human nucleus
Reference:
Morton, N,E. (1991). Parameters of the human genome. Proc. Natl. Acad. Sci. USA 88, 7474-7476. [PubMed] [Full text]

Gene number and organization
Table: 1-3, 1-4, 1-5.
Reference:
Miklos, G.L. and Rubin, G.M. (1996). The role of the genome project in determining gene function: insights from model organisms. Cell 86, 521-429.  [PubMed]
Adams, M.D. et al. (2000). The genome sequence of Drosophila melanogaster. Science 287, 2185-2195. [PubMed]
Additional reference:
The ENCODE Project Consortium. (2011). A User's Guide to the Encyclopedia of DNA Elements (ENCODE). PLoS 9, e1001046. [PubMed]
Finnegan, D.J. (2012). Retrotransposons. Curr. Biol. 22, R432-437. [PubMed]
International Human Genome Sequencing Consortium (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921. [PubMed] [Full text]
Little, P.F. (2005). Structure and function of the human genome. Genome Res. 15, 1759-1766. [PubMed]
Venter, J.C. et al. (2001). The sequence of the human genome. Science 291, 1304-1351. [PubMed]
Web link:
http://www.wormbase.org/ The worm genome.
http://flybase.bio.indiana.edu/ The Drosophila genome.
http://www.genome.gov/page.cfm?pageID=10001694  The human genome.
http://www.nature.com/genomics/ Nature's Genome Gateway.
http://www.reactome.org/ A curated resource of core pathways and reactions in human biology.

Regulatory networks: redundant, robust, and noisy
Reference:
Cyert, M.S. (2001). Regulation of nuclear localization during signaling. J. Biol. Chem. 276, 20805-20808. [Full text]
Elena, S.F. and Lenski, R.E. (1997). Test of synergistic interactions among deleterious mutations in bacteria. Nature 390, 395-398. [PubMed]
Brugge, J.S. and McCormick, F. (1999). Cell regulation: intracellular networking. Curr. Opin. Cell Biol. 11, 173-176.
Weng, G., Bhalla, U.S. and Iyenger, R. (1999). Complexity in biological signaling systems. Science 284, 92-96. [PubMed]
Eisenberg, D., Marcotte, E.M., Xenarios, I. and Yeates, T.O. (2000). Protein function in the post-genomic era. Science 405, 823-826. [PubMed]
Additional reference:
Almaas, E., Kovacs, B., Vicsek, T., Oltvai, Z.N. and Barabasi, A.L. (2004).  Global organization of metabolic fluxes in the bacterium Escherichia coli.  Nature 427, 839-843.  [PubMed]
Eldar, A., and Elowitz, M.B. (2010). Functional roles for noise in genetic circuits. Nature 467, 167-173. [PubMed]
Guantes, R., Rastrojo, A., Neves, R., Lima, A., Aguado, B., and Iborra, F.J. (2015). Global variability in gene expression and alternative splicing is modulated by mitochondrial content. Genome Res. 25, 633-644. [PubMed]
Hartman, J.L., Garvik, B. and Hartwell, L. (2001). Principles for the buffering of genetic variation. Science 291, 1001-1004.  [PubMed]
Huh, W.K., Falvo, J.V., Gerke, L.C., Carroll, A.S., Howson, R.W., Weissman, J.S. and O'Shea. (2003).  Global analysis of protein localization in budding yeast.  Nature 425, 686-691.  [PubMed]
Kondo, S., and Miura, T. (2010). Reaction-diffusion model as a framework for understanding biological pattern formation. Science 329, 1616-1620. [PubMed]
Lestas, I., Vinnicombe, G., and Paulsson, J. (2010). Fundamental limits on the suppression of molecular fluctuations. Nature 467, 174-178. [PubMed]
Phillips, R., and Milo, R. (2009). A feeling for the numbers in biology. Proc. Natl. Acad. Sci. USA 106, 21465-21471. [PubMed]
Raj, A., and van Oudenaarden, A. (2008). Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135, 216-226. [PubMed]
Seebacher, J., and Gavin, A.C. (2011). SnapShot: protein-protein interaction networks. Cell 144, 1000. [PubMed]
Stelling, J., Sauer, U., Szallasi, Z. and Doyle, F.J. (2004).  Robustness of cellular functions.  Cell 118, 675-685.  [PubMed]
Tanner, J.M., and Rutter, J. (2016). You are what you eat… or are you? Dev. Cell 36, 483-485. [PubMed]
Vidal, M., Cusick, M.E., and Barabási, A.L. (2011). Interactome networks and human disease. Cell 144, 986-998. [PubMed]
Web link:
http://www.systems-biology.org/ A portal for systems biology; go to 'CellDesigner' to see some complex pathways.
http://bionumbers.hms.harvard.edu/ Database of useful biological numbers.

Box 1-8. Protein:protein interactions - 'two-hybrid', 'FRET'
Reference:
Fields, S. and Song, O. (1989). A novel genetic system to detect protein-protein interactions. Nature 340, 245-246. [PubMed]
Selvin, P.R. (1995). Fluorescence resonance energy transfer. Methods Enzymol. 246, 300-334.
Tsien, R.Y. and Miyawaki, A. (1998). Seeing the machinery of live cells. Science 280, 1954-1955.  [PubMed]
Walhout, A.J.M., Sordella, R., Lu, X., Hartley, J.L., Temple, G.F., Brasch, M.A., Thierry-Mieg, N. and Vidal, M. (2000). Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287, 116-122. [PubMed]
Additional reference:
Sekar, R.B. and Periasamy, A. (2003).  Fluorescence resonance energy transfer (FRET) microscopy imaging of live cell protein localizations.  J. Cell Biol. 160, 629-633.  [PubMed]
Tinoco, I. Jr., and Gonzalez, R.L. Jr. (2011). Biological mechanisms, one molecule at a time. Genes Dev 25, 1205-1231. [PubMed]
Vidal, M., and Fields, S. (2014). The yeast two-hybrid assay: still finding connections after 25 years. Nat Methods 11, 1203-1206. [PubMed]
Web link:
http://www.probes.com/handbook/boxes/0422.html   FRET page from a supplier.

Box 1-9. Simulating complex control circuits
Reference:
Barkal, N. and Leibler, S. (1997). Robustness in simple biochemical networks. Nature 387, 913-917. [PubMed]
Noble, D. (2002).  The rise of computational biology.  Nat. Rev. Mol. Cell Biol. 3, 459-463.  [PubMed]
Weng, G., Bhalla, U.S. and Iyenger, R. (1999). Complexity in biological signaling systems. Science 284, 92-96. [PubMed]
Additional reference:
Ajo-Franklin, C.M., Drubin, D.A., Eskin, J.A., Gee, E.P., Landgraf, D., Phillips, I., and Silver, P.A. (2007). Rational design of memory in eukaryotic cells. Genes Dev. 21, 2271-2276. [PubMed]
Berg, H.C. (2008). Bacterial flagellar motor. Curr. Biol. 18, R689-691. [PubMed]
Blais, A. and Dynlacht, B.D. (2005).  Constructing transcriptional regulatory networks.  Genes Dev. 19, 1499-1511. [PubMed]
Drubin, D.A.., Way, J.C., and Silver, P.A. (2007). Designing biological systems. Genes Dev. 21, 242-254. [PubMed]
Rao, C.V., Kirby, J.R. and Arkin, A.P. (2004).  Design and Diversity in Bacterial Chemotaxis: A Comparative Study in Escherichia coli and Bacillus subtilis.  PLoS Biol. 2, e49.  [PubMed]
Raser, J.M. and O'Shea, E.K. (2005).  Noise in gene expression: origins, consequences, and control.  Science 309, 2010-2023.  [PubMed]
von Dassow, G., Meir, E., Munro, E.M. and Odell, G.M. (2000). The segment polarity network is a robust developmental module. Nature 406, 188-192. [PubMed]
Various authors (2002) in 'Modelling Complex Biological Systems', a special edition of BioEssays 24 (12), December 2002. [Full text]
Vilar, J.M., Guet, C.C. and Leibler, S. (2003).  Modeling network dynamics: the lac operon, a case study.  J. Cell Biol. 161, 471-476.  [PubMed]

Sub-compartments and the origin of nuclei
Figure: 1-17.
Reference:
Gould, G.W. and Dring, G.J. (1979). On a possible relationship between bacterial endospore formation and the origin of eukaryotic cells. J. Theor. Biol. 81, 47-53.
Cavalier-Smith, T. (1988). Origin of the cell nucleus. BioEssays 9, 72-78.
Sogin, M.L. (1991). Early evolution and the origin of eukaryotes. Curr. Opin. Genet. Dev. 1, 457-463. [PubMed]
Lake, J.A. and Rivera, M.C. (1994). Was the nucleus the first endosymbiont? Proc. Nat. Acad. Sci. USA 91, 2880-2881. [Full text]
Bendich, A.J. and Drlica, K. (2000). Prokaryotic and eukaryotic chromosomes: what's the difference? BioEssays 22, 481-486. [PubMed]
Additional reference:
An, S., Kumar, R., Sheets, E.D., and Benkovic, S.J. (2008). Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320, 103-106. [PubMed]
Bendich, A.J. (2007). The size and form of chromosomes are constant in the nucleus, but highly variable in bacteria, mitochondria and chloroplasts. Bioessays 29, 474-483. [PubMed]
Dacks, J.B., Field, M.C., Buick, R., Eme, L., Gribaldo, S., Roger, A.J., Brochier-Armanet, C., and Devos D.P. (2016). The changing view of eukaryogenesis - fossils, cells, lineages and how they all come together. J Cell Sci 129, 3695-3703. [PubMed]
Fuerst, J.A. (2005). Intracellular compartmentation in planctomycetes. Annu. Rev. Microbiol. 59, 299-328. [PubMed]
Chan, Y.H., and Marshall, W.F. (2012). How cells know the size of their organelles. Science 337, 1186-1189. [PubMed]
Wilson, K.L., and Dawson, S.C. (2011). Functional evolution of nuclear structure. J. Cell Biol. 195, 171-181. [PubMed]

Box 1-10. The three primary lineages of the living world
Reference:
Gray, M.W. (1992). The endosymbiont hypothesis revisited. Int. Rev. Cytol. 141, 233-355.
Gray, M.W. (1996). A third form of life. Nature 383, 299-300.
Martin, W. and Müller, M. (1998). The hydrogen hypothesis for the first eukaryote. Nature 392, 37-41. [PubMed]
Additional reference:
de Duve, C. (2007). The origin of eukaryotes: a reappraisal. Nat. Rev. Genet. 8, 395-403. [PubMed]
Simpson, A.G. and Roger, A.J. (2004).  The real 'kingdoms' of eukaryotes.  Curr. Biol. 14, R693-696.  [PubMed]
Szostak, J.W. (2009). Origins of life: systems chemistry on early earth. Nature 459, 171-172. [PubMed]

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