Analysisof regulation of the eukaryotic
the laboratory is to understand, analyze, and study the regulation ofeukaryotic cell growth and division. The work is
carried forward in a numberof directions:
1.The control of phosphorylation
of the retinoblastoma protein is being analyzedunder
conditions where the normal division cycle is analyzed and perturbationsof the cell cycle are minimized. We find
that contrary to current belief,a
phosphorylation-dephosphorylation of the Rb protein is not required duringthe
mammalian division cycle. See Cooper, Yu, and Shayman,IUBMB (1999), and Cooper and Shayman.
Cell and Molecular Life Sciences(2001) below.
2.Time lapse videography is
being pursued in order to analyze the methodscurrently
being used to synchronize cells. Our results indicate that variousstarvation and inhibition methods do not
synchronize cells. These resultssupport theoretical
analyses of synchronization methods. See Cooper, CellBiology
International (2002) below.
3.We are studying the expression of BRCA1 protein
during the division cycleand its phosphorylation pattern in order to understand how it is regulatedduring the division cycle.
4.We are studying the expression of
various cyclins during the normal divisioncycle in order to reexamine the current view of cyclin biogenesis and control.We
are comparing results from two-color flow cytometric
analysis with directbiochemical analysis in order
to see whether localization of cyclins canaccount for the observed results.
5. We are reanalyzing publicly
available data from Microarray analysis inorder to see whether proposals of G1-phase gene
expression are statisticallysignificant. See Shedden and Cooper, PNAS (2002) and Shedden
andCooper, Nucleic Acids Research (2002) below.
Cooper,S. 1979. A unifying model for the G1
period in prokaryotes and eukaryotes.Nature
Cooper,S. 1987. G(0)
and Cell Cycle Controls. Bioessays 7:220-223.
Cooper,S. 1997. Division Pattern of a Round
Mutant of Escherichia coli.J.
Cooper,S. 1997. DNA Replication: the 30th
Anniversary of the Bacterial Modeland the
"Baby Machine". TIBS; 22:490-494.
Cooper,S. 1998. On the proposal on a G0 phase
and the Restriction Point.FASEB J.
Cooper,S.1998. On the Interpretation of
the Shortening of the G1-phase byOverexpression of Cyclins in Mammalian Cells. Exp.Cell Res. 238:110-115 .
Cooper,S. 1998. Mammalian Cells are Not
Synchronized in G1 Phase by Starvationor
Inhibition: Considerations of the Fundamental Concept of G1-phase Synchronization.CellProlif. 31:9-16.
Cooper,S. 1998. Length Extension in Growing
Yeast: Is Growth Exponential?Yes.Microbiology.
Cooper,S. and Keasling,
J. D. 1998. Cycle-specific Replication of Chromosomaland
F-plasmid Origins. FEMS Micro. Lett.
1999. The Continuum Model and G1-Control of the Mammalian Cell Cycle.in progress in Cell Cycle Research. Vol. 4.
Chapter 3 (L. Meijer,S. Guidet, and M. Philippe, eds.) Plenum Press,
Yu, C. and Shayman, J.A. 1999. Phosphorylation-Dephosphorylationof
Retinoblastoma Protein is Not Necessary for Passage Through the MammalianDivision Cycle. IUBMB-Life. 48:225-230.
Cooper,S. 2000. Toward a Standard System for
the Mammalian Cycle. ASM News66:71-75(copyrighted by the American
Society for Microbiology and reprinted bypermission
of ASM News).
Cooper,S., and Shayman,
J.A. 2001. Revisiting Retinoblasoma Phosphorylationduring the Mammalian Cell
Cycle. Cellular and MolecularLife
Cooper,S. 2001. Revisiting the
Relationship of the Mammalian G1Phase to Cell Differentiation. J. Theor. Biol. 208:399-402.
Cooper,S. 2001 Helical Growth and the Shape of
Vibrio Cholerae. FEMS
Cooper,S. 2001. Size, Volume, Length and the
Control of the Bacterial DivisionCycle.
Microbiology. Microbiology 147: 2629-2630; also page2632.
Shedden,K. and Cooper,
S. 2002. Analysis of Cell-Cycle-SpecificGene
Expression in Human Cells as Determined by Microarrays.
Proc.Natl. Acad.Sci. USA 99:4379-4384.
Cooper,S. 2002. Reappraisal of G1-phase
arrest and synchronization bylovastatin. Cell
Biol. Int. 27:715-727.
Cooper,S. 2002. Minimally Disturbed,
Multi-Cycle, and Reproducible Synchronyusing a
Eukaryotic "Baby Machine" Bioessays.
Cooper,S. 2002. The
Schaechter-Bentzon-Maaløe experiment and the analysisof cell cycle events in
eukaryotic cells. Trends in Microbiology. 10:169-173. (reprinted
with permission from Elsevier Science. The Home page of Trends in
Microbiology is http://www.elsevier.com/locate/tim . Singlecopies of the article can be downloaded and printed
for the reader's personalrsearch and study.
Shedden,K. and Cooper, S. 2002. Analysis of
Cell-Cycle Gene Expressionin S. cerevisiae
Using Microarrays and Multiple Synchronization Methods.Nucleic Acids Research. 30: 2920-2929
Cooper,S. 2002. Cell cycle analysis and microarrays ,
Trends in Genetics. 18:289-290
Cooper,S. 2002. Cell Biology Moves Forward in
2050. ASM News. 68:260-261.
Cooper,S. 2003. Rethinking
synchronization of mammalian cellsfor cell cycle
analysis. Cellular and Molecular Life Sciences 6:1099-1106
Cooper,S. 2003. Reappraisal of Serum Starvation, the
Restriction Point, G0,and G1-phase Arrest
Points. FASEB J. 17:333-340
Cooper,S. 2003 How the change
from FLM to FACS affected our understandingof the
G1 phase of the cell cycle. Cell Cycle. 2:157-159
Cooper,S. and Shedden, K. 2003. Microarray
Analysis of Gene Expression duringthe Cell
Cycle. Cell & Chromosome, 2:1.
Cooper,S. The Continuum Model: Regulation of
the mammalian cell cycle is relatedto a continuous
accumulation process and not dependent on phase-specificcascades
of gene expression. Mathematical Biosciences Institute Workshop,Ohio State University, Columbus, Ohio. September
29-October 3, 2003.
Cooper,S. 2004. The Ideas of Ludwik Fleck and Their Application to theEukaryotic
Cell Cycle, the Restriction Point, and G1-phase Control In Preparation
Cooper,S. and Keasling,
J. D. 2004. Experimental and theoretical considerationsof
P1-plasmid replication and segregation during the E. coli cell cycle. Journal
of Biological Sciences. 5:222-229
Cooper,S. 2004. The
Continuum Model of the Eukaryotic Cell Cycle: Applicationto
G1-phase control, Rb phosphorylation,
Microarray Analysis of Gene Expression,and Cell Synchronization. Clinical Oncology.
four articles constitute a debate regarding the efficacy of whole culture
Cooper,S. 2004. Is whole-culture
synchronization biology's ‘perpetual-motionmachine’?
Trends in Biotechnology 22: 266-269
Spellman, P. T. and Gavin Sherlock, G.
2004. Reply: whole-culturesynchronization ? effective tools for cell cycle studies Trends inBiotechnology 22: 270-273
Cooper, S. 2004
Rejoinder: whole-culture synchronization cannot, and does not,synchronize
cells Trends in Biotechnology 22: 274-276
Spellman, P. T
and Sherlock , G. 2004. Final words: cell age and
cell cycle are unlinked Trends in Biotechnology 22: 277-278
Cooper, S. 2004.
Reanalysis of the protocol for in vitro synchronization ofmammalian
astrocytic cultures by serum deprivation. Brain
Research Protocols. 15:115-118
2004. Control of and Maintenance of Mammalian Cell Size BMC Cell Biology. 5:35
2004. On the persistence of Whole-Culture Synchronizationfor
cell-cycle analysis. in preparation
2004. Bacterial Growth and Division. Article in Encyclopediaof
Molecular Cell Biology and Molecular Medicine. Wiley-VCH. Volume
S. 2005 Comment on and reply to “Analysis
of variation of amplitudes in cell cycle gene expression” by Liu, Gaido and Wolfinger: On the
analysis of gene expression during the normal, eukaryotic, cell cycle
Theoretical Biology and Medical Modeling. 2:47
Cooper, S., Iyer, G., Tarquini, M., and Bissett , P. 2006, Nocodazole does not
synchronize mammalian cells. Cell and Tissue Research, 324:237-242
Cooper, S. 2006 Distinguishing between linear and
exponential cell growth during the division cycle: Single-cell studies,
cell-culture studies, and the object of cell-cycle research. Theoretical
Biology and Medical Modeling. 3:10
Cooper, S. 2006. Checkpoints and Restriction Points in
Bacteria and Eukaryotic Cells. Bioessays. Accepted
Cooper, S. 2006. Regulation of DNA synthesis in bacteria:
Analysis of the Bates/Kleckner
licensing/initiation-mass model for cell-cycle control. Molecular Microbiology, Accepted for publication.
S. 2006. TheContinuum Manifesto. Manuscript in Preparation.
Inaddition to these papers, much of this work is analyzed
in detail in thebook:
Growth and Division, Biochemistry and Regulation of Prokaryoticand
Eukaryotic Division Cycles, Academic press. 1991.