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Journal of Biological Physics

, Volume 27, Issue 4, pp 329–359 | Cite as

DNA Replication and Cell Cycle Progression Regulatedby Long Range Interaction between Protein Complexes bound to DNA

  • Leif Matsson
Article

Abstract

A nonstationary interaction that controlsDNA replication and the cell cycle isderived from many-body physics in achemically open T cell. The model predictsa long range force F′(ξ) =– (κ/2) ξ(1 – ξ)(2 – ξ)between thepre-replication complexes (pre-RCs) boundby the origins in DNA, ξ = ϕ/N being the relativedisplacement of pre-RCs, ϕ the number of pre-RCs, N the number of replicons to be replicated,and κ the compressibilitymodulus in the lattice of pre-RCs whichbehaves dynamically like an elasticallybraced string. Initiation of DNAreplication is induced at the thresholdϕ = N by a switch ofsign of F′'(ξ), fromattraction (–) and assembly in the G1 phase (0<ϕ<N), to repulsion (+) and partialdisassembly in the S phase (N< ϕ < 2N), withrelease of licensing factors from pre-RCs,thus explaining prevention ofre-replication. Replication is terminatedby a switch of sign of force at ϕ = 2N, from repulsion inS phase back to attraction in G2, when all primed replicons havebeen duplicated once. F′(0) = 0corresponds to a resting cell in theabsence of driving force at ϕ= 0. The model thus ensures that the DNAcontent in G2 cells is exactlytwice that of G1 cells. The switch of interaction at the R-point, at which N pre-RCs have been assembled, starts the release of Rb protein thus also explaining the shift in the Rb phosphorylation from mitogen-dependent cyclinD to mitogen-independent cyclin E.Shape,slope and scale of the response curvesderived agree well with experimental datafrom dividing T cells and polymerising MTs,the variable length of which is due to anonlinear dependence of the growthamplitude on the initial concentrations oftubulin dimers and guanosine-tri-phosphate(GTP). The model also explains the dynamic instabilityin growing MTs.

Cell cycle DNA replication cyclin kinases DNA origin recognition complex microtubules DNA duplex Rb protein p27 licensing factor origin recognition complex 

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© Kluwer Academic Publishers 2001

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  • Leif Matsson

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