Matsson L
J Biol Phys. 2001 Dec;27(4):329-59. doi: 10.1023/A:1014288212898.
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 G(1) 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 G(2), 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 G(2) cells is exactlytwice that of G(1) 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.
一种控制DNA复制和细胞周期的非平稳相互作用源自化学开放的T细胞中的多体物理学。该模型预测，在DNA中由复制起点结合的复制前复合物（pre-RC）之间存在长程力F'(ξ)= - (κ/2) ξ(1 - ξ)(2 - ξ)，其中ξ = ϕ/N是pre-RC的相对位移，ϕ是pre-RC的数量，N是待复制的复制子数量，κ是pre-RC晶格中的压缩模量，其动态行为类似于弹性支撑的弦。DNA复制的起始是在阈值ϕ = N时通过F''(ξ)符号的切换诱导的，从G(1)期（0 < ϕ < N）的吸引（-）和组装，到S期（N < ϕ < 2N）的排斥（+）和部分解离，同时pre-RC释放许可因子，从而解释了防止再复制的现象。当所有已引发的复制子都被复制一次后，在ϕ = 2N时力的符号切换会终止复制，从S期的排斥回到G(2)期的吸引。F'(0) = 0对应于在ϕ = 0时没有驱动力的静止细胞。因此，该模型确保G(2)期细胞中的DNA含量恰好是G(1)期细胞的两倍。在R点（此时已组装了N个pre-RC）相互作用的切换会引发Rb蛋白的释放，这也解释了Rb磷酸化从依赖有丝分裂原的细胞周期蛋白D向不依赖有丝分裂原的细胞周期蛋白E的转变。所推导的响应曲线的形状、斜率和尺度与来自分裂T细胞和聚合微管（MT）的实验数据非常吻合，MT的可变长度归因于生长幅度对微管蛋白二聚体和鸟苷三磷酸（GTP）初始浓度的非线性依赖。该模型还解释了生长中的MT的动态不稳定性。
